pkaC

id: P34099
gene_symbol: pkaC
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: pkaC encodes the single catalytic (C) subunit of cAMP-dependent protein
  kinase (PKA) in Dictyostelium discoideum, an AGC-family serine/threonine protein
  kinase (EC 2.7.11.11). It is unusually large (648 aa, ~73 kDa) relative to metazoan
  PKA-C, owing to an extended low-complexity N-terminal region that precedes a canonical
  C-terminal catalytic domain. The catalytic subunit is held inactive in a holoenzyme
  with a single regulatory (R) subunit (pkaR); binding of cAMP to the R subunit releases
  the active C subunit, which then phosphorylates serine/threonine residues on target
  proteins. PKA is the principal intracellular effector of cAMP and a master regulator
  of the starvation-induced multicellular developmental program. PKA activity is low
  in growing amoebae, rises during aggregation, and peaks at culmination. It is required
  for aggregation and for expression of aggregation-stage and prespore genes, governs
  the prestalk/stalk versus prespore/spore differentiation decisions, and, as intracellular
  cAMP set by adenylyl cyclases (ACA/ACG/ACR) and the phosphodiesterase RegA rises,
  triggers culmination and the terminal maturation of both spore and stalk cells. Beyond
  development, active PKA acts within the cAMP-relay oscillator as a negative-feedback
  element (acting on ERK2, adenylyl cyclase and the CAR1 receptor), contributes to
  spatiotemporal control of chemotactic signaling through Ras/Rap1/TORC2, and mediates
  shutdown of macropinocytosis at the growth-to-development transition.
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference of cytosolic localization. The active, dissociated
      catalytic subunit acts in the cytosol (and nucleus), consistent with its role
      as a soluble kinase.
    action: ACCEPT
    reason: Cytosol is a genuine site of action for the released catalytic subunit,
      consistent with direct evidence that a large fraction of the enzyme is recovered
      as dissociated regulatory and catalytic subunits. This is a location, not the
      core molecular function.
    supported_by:
    - reference_id: PMID:26485773
      supporting_text: the rest is recovered in the form of dissociated regulatory
        and catalytic subunits that were purified
- term:
    id: GO:0005952
    label: cAMP-dependent protein kinase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: The catalytic subunit is part of the PKA holoenzyme, a dimer of one regulatory
      and one catalytic subunit that dissociates upon cAMP binding. This is a core
      annotation.
    action: ACCEPT
    reason: Directly established biochemically for the Dictyostelium enzyme; the holoenzyme
      is an R-C dimer, and cAMP releases the active C subunit.
    supported_by:
    - reference_id: PMID:26485773
      supporting_text: The CAMP-dependent holoenzyme is a dimer consisting of one regulatory
        and one catalytic subunit
- term:
    id: GO:0007189
    label: adenylate cyclase-activating G protein-coupled receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference placing PKA in cAMP/GPCR signaling. PKA is the
      key intracellular effector of cAMP produced downstream of the cAR1 GPCR and adenylyl
      cyclase. A more specific Dictyostelium term is separately annotated (GO:0140582).
    action: KEEP_AS_NON_CORE
    reason: PKA participates in cAMP GPCR signaling as a downstream effector, but this
      broad pathway term is a downstream biological process rather than the core molecular
      function.
    supported_by:
    - reference_id: PMID:9843585
      supporting_text: A rise in the internal concentration of cAMP activates protein
        kinase A
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: cAMP-dependent protein kinase activity is the defining, experimentally
      established molecular function of pkaC and is broadly supported across orthologs.
    action: ACCEPT
    reason: This is the core molecular function; the catalytic subunit is a bona fide
      cAMP-dependent Ser/Thr kinase whose activity is inhibited by the regulatory subunit
      and relieved by cAMP.
    supported_by:
    - reference_id: PMID:8373760
      supporting_text: PkaC copurifies with cAPK activity
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based general protein kinase activity. Correct but less informative
      than the specific cAMP-dependent protein kinase activity term.
    action: KEEP_AS_NON_CORE
    reason: Accurate parent term derived from the protein kinase domain, but the specific
      child GO:0004691 better captures the core function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based Ser/Thr kinase activity. Correct but general relative to
      cAMP-dependent protein kinase activity.
    action: KEEP_AS_NON_CORE
    reason: PKA is a Ser/Thr kinase, so this is accurate; the specific term GO:0004691
      is preferred for the core function.
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: EC 2.7.11.11 mapping to cAMP-dependent protein kinase activity, matching
      the UniProt catalytic activity annotation.
    action: ACCEPT
    reason: Electronic assignment that correctly recapitulates the core molecular function.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ATP binding inferred from the protein kinase ATP-binding site. A required
      substrate-binding property supporting catalysis.
    action: KEEP_AS_NON_CORE
    reason: ATP binding is a correct, mechanistically necessary property of the kinase
      but is subordinate to the catalytic activity that defines the function.
- term:
    id: GO:0009653
    label: anatomical structure morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Very general ARBA machine-learning morphogenesis term. PKA is genuinely
      required for fruiting body (sorocarp) morphogenesis, but this broad term is uninformative
      and more specific terms (e.g. sorocarp morphogenesis) are separately annotated.
    action: KEEP_AS_NON_CORE
    reason: Correct at a high level given PKA's developmental role, but too general;
      the specific GO:0031288 sorocarp morphogenesis annotation is preferred.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Rhea/reaction-based protein serine kinase activity, consistent with the
      Ser-phosphorylation reaction annotated in UniProt.
    action: KEEP_AS_NON_CORE
    reason: Accurate reaction-derived MF; the specific cAMP-dependent protein kinase
      activity term captures the core function.
- term:
    id: GO:0031154
    label: culmination involved in sorocarp development
  evidence_type: IDA
  original_reference_id: PMID:21534947
  qualifier: involved_in
  review:
    summary: PKA activity is required for culmination; PKA-null cells arrest at the
      slug stage and cannot culminate, and forcing PKA activity drives terminal differentiation.
      This is a genuine developmental role of pkaC.
    action: ACCEPT
    reason: Culmination dependence on PKA is well established experimentally; the catalytic
      subrole in triggering terminal differentiation at culmination is a defining developmental
      function.
    supported_by:
    - reference_id: PMID:1332055
      supporting_text: properly regulated PKA activity is essential for culmination
- term:
    id: GO:0140676
    label: oscillatory cAMP signaling
  evidence_type: IDA
  original_reference_id: PMID:9843585
  qualifier: involved_in
  review:
    summary: PKA is an essential negative-feedback element of the cAMP-relay oscillator
      network, inhibiting ERK2 and CAR1 ligand binding once internal cAMP rises.
    action: KEEP_AS_NON_CORE
    reason: PKA is required for the oscillatory network, but this is a downstream systems-level
      process rather than the core molecular function.
    supported_by:
    - reference_id: PMID:9843585
      supporting_text: A rise in the internal concentration of cAMP activates protein
        kinase A such that it inhibits ERK2 and leads to a loss-of-ligand binding by
        CAR1
- term:
    id: GO:0007264
    label: small GTPase-mediated signal transduction
  evidence_type: IMP
  original_reference_id: PMID:28302905
  qualifier: involved_in
  review:
    summary: PKA controls chemoattractant signaling in part by regulating the small
      GTPases RasG and Rap1 (and TORC2). Cells lacking PKA show upregulated and spatially
      misregulated RasG/Rap1 activity.
    action: KEEP_AS_NON_CORE
    reason: PKA acts upstream of RasG/Rap1 signaling during chemotaxis; this is a downstream
      regulatory role rather than the core kinase function.
    supported_by:
    - reference_id: PMID:28302905
      supporting_text: PKA controls chemoattractant signal transduction, in part, through
        the regulation of RasG, Rap1 and TORC2
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:12392578
  qualifier: enables
  review:
    summary: PKA activity directly measured by phosphorylation of the PKA-specific
      substrate Kemptide, confirming the core catalytic function.
    action: ACCEPT
    reason: Direct biochemical measurement of PKA catalytic activity supports the core
      molecular function.
    supported_by:
    - reference_id: PMID:12392578
      supporting_text: PKA activity, measured by phosphorylation of the PKA-specific
        substrate Kemptide
- term:
    id: GO:0140986
    label: G protein-coupled chemorepellent receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:30462573
  qualifier: acts_upstream_of_or_within
  review:
    summary: PKA is required for AprA-mediated chemorepulsion; pkaC-null cells fail
      to move away from the secreted chemorepellent AprA, which signals through the
      GrlH GPCR.
    action: KEEP_AS_NON_CORE
    reason: PKA is a required component of the chemorepellent signaling pathway, but
      this is a downstream biological process, not the core molecular function.
    supported_by:
    - reference_id: PMID:30462573
      supporting_text: AprA uses a subset of chemoattraction signal transduction pathways
        including Ras, protein kinase A, target of rapamycin (TOR), phospholipase A,
        and ERK1
- term:
    id: GO:0043327
    label: chemotaxis to cAMP
  evidence_type: IMP
  original_reference_id: PMID:28302905
  qualifier: involved_in
  review:
    summary: Cells lacking PKA display severe cAMP chemotaxis defects including impaired
      directional sensing, establishing a required role for PKA in cAMP chemotaxis.
    action: KEEP_AS_NON_CORE
    reason: PKA is essential for cAMP chemotaxis, but this behavioral process is downstream
      of PKA's core catalytic function.
    supported_by:
    - reference_id: PMID:28302905
      supporting_text: cells lacking PKA display severe chemotaxis defects, including
        impaired directional sensing
- term:
    id: GO:0071964
    label: establishment of cell polarity regulating cell shape
  evidence_type: IMP
  original_reference_id: PMID:28302905
  qualifier: involved_in
  review:
    summary: PKA restricts the site and extent of chemotactic pathway activation and
      thereby pseudopod protrusion, contributing to cell polarity and shape during
      chemotaxis.
    action: KEEP_AS_NON_CORE
    reason: Supported by the pkaC-null chemotaxis phenotype, but this is a downstream
      cell-biological consequence of PKA signaling.
    supported_by:
    - reference_id: PMID:28302905
      supporting_text: plays a key role in restricting the extent, as well as the site,
        of chemotactic pathway activation and, thereby, pseudopod protrusion
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IC
  original_reference_id: PMID:1330484
  qualifier: enables
  review:
    summary: ATP binding inferred by curators from the demonstrated cAMP-dependent
      protein kinase activity. A mechanistically required property.
    action: KEEP_AS_NON_CORE
    reason: Correct inference from kinase activity; subordinate to the core catalytic
      function.
- term:
    id: GO:0019887
    label: protein kinase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:28302905
  qualifier: enables
  review:
    summary: This casts PKA's regulation of the RasG/Rap1/TORC2/PKB signaling network
      as a molecular-function "protein kinase regulator activity." PKA regulates these
      pathways through its own kinase activity, making this an over-interpretation
      of a downstream biological effect as a distinct molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The regulatory effects on other kinases are mediated by PKA's catalytic
      activity and are downstream biological processes; assigning a separate "protein
      kinase regulator activity" MF conflates process with molecular function.
    supported_by:
    - reference_id: PMID:28302905
      supporting_text: PKA controls chemoattractant signal transduction, in part, through
        the regulation of RasG, Rap1 and TORC2
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IMP
  original_reference_id: PMID:28302905
  qualifier: involved_in
  review:
    summary: Dictyostelium-specific cAMP chemoattractant receptor signaling pathway
      term; PKA is a required, spatiotemporally regulating component of cAR1/ACA-driven
      cAMP signaling.
    action: KEEP_AS_NON_CORE
    reason: Well supported by the pkaC-null phenotype, but this is a downstream signaling
      pathway rather than the core molecular function.
    supported_by:
    - reference_id: PMID:28302905
      supporting_text: PKA is necessary for proper spatiotemporal regulation of early
        chemoattractant signal transduction pathways
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IMP
  original_reference_id: PMID:9020088
  qualifier: involved_in
  review:
    summary: PKA is an important regulator of ERK2 activation and adaptation and lies
      downstream of ERK2 in mediating PKA function during aggregation and development.
    action: KEEP_AS_NON_CORE
    reason: PKA participates in the ERK2 MAPK module as a regulator, a downstream process
      role rather than the core catalytic function.
    supported_by:
    - reference_id: PMID:9020088
      supporting_text: Ras and cAMP-dependent protein kinase (PKA), are important regulators
        of ERK2 activation and adaptation
- term:
    id: GO:0019887
    label: protein kinase regulator activity
  evidence_type: IMP
  original_reference_id: PMID:9020088
  qualifier: enables
  review:
    summary: Assigns "protein kinase regulator activity" MF based on PKA's genetic
      effect on ERK2 activation/adaptation. This regulation is mediated by PKA's own
      kinase activity and is a downstream process, not a distinct molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: PKA's influence on ERK2 is an indirect, signaling-level effect; the core
      MF is its kinase activity, and a separate protein-kinase-regulator MF over-interprets
      the phenotype.
    supported_by:
    - reference_id: PMID:9020088
      supporting_text: Ras and cAMP-dependent protein kinase (PKA), are important regulators
        of ERK2 activation and adaptation
- term:
    id: GO:0004860
    label: protein kinase inhibitor activity
  evidence_type: IMP
  original_reference_id: PMID:8670837
  qualifier: enables
  review:
    summary: Based on PKA being required for adaptation (attenuation) of the ERK2 response.
      "Protein kinase inhibitor activity" as a molecular function implies direct stoichiometric
      inhibition of a kinase (as by a PKI protein); PKA's effect on ERK2 is indirect
      and mediated by its own catalytic activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: The genetic requirement of PKA for ERK2 adaptation does not establish a
      direct protein-kinase-inhibitor molecular function; this over-interprets a downstream
      inhibitory signaling effect.
    supported_by:
    - reference_id: PMID:8670837
      supporting_text: Intracellular cAMP and cAMP-dependent protein kinase (PKA) are
        essential for adaptation of the ERK2 response
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11270120
  qualifier: enables
  review:
    summary: PKA directly phosphorylates a serine site in the gdt1 protein in vitro,
      demonstrating protein serine kinase activity on a physiological substrate.
    action: KEEP_AS_NON_CORE
    reason: Directly demonstrated Ser-kinase activity; accurate but the specific cAMP-dependent
      protein kinase activity term is preferred for the core function.
    supported_by:
    - reference_id: PMID:11270120
      supporting_text: found that one of them is efficiently phosphorylated by PKA
        in vitro
- term:
    id: GO:0005952
    label: cAMP-dependent protein kinase complex
  evidence_type: IDA
  original_reference_id: PMID:26485773
  qualifier: part_of
  review:
    summary: Directly demonstrated that the catalytic subunit forms the PKA holoenzyme
      with the regulatory subunit as an R-C dimer.
    action: ACCEPT
    reason: Core annotation established by biochemical reconstitution of the holoenzyme
      from purified subunits.
    supported_by:
    - reference_id: PMID:26485773
      supporting_text: The CAMP-dependent holoenzyme is a dimer consisting of one regulatory
        and one catalytic subunit
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:29704004
  qualifier: involved_in
  review:
    summary: PKA is required for spore-gene transcription; the transcription factor
      SpaA activates (pre)spore promoters in a PKA-dependent manner, placing PKA upstream
      of spore-gene transcriptional control.
    action: KEEP_AS_NON_CORE
    reason: PKA regulates developmental transcription indirectly via downstream transcription
      factors; a real but downstream role rather than the core molecular function.
    supported_by:
    - reference_id: PMID:29704004
      supporting_text: SpaA dependent spore gene expression required PKA in vivo and
        was stimulated in vitro by the membrane-permeant PKA agonist 8Br-cAMP
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:10772794
  qualifier: involved_in
  review:
    summary: PKA is a major activator of discoidin (discoidin I gamma) expression during
      growth and the growth-to-development transition; pkaC-null cells show reduced
      discoidin expression.
    action: KEEP_AS_NON_CORE
    reason: Genuine positive regulatory role in developmental gene expression, but
      downstream of the core kinase function.
    supported_by:
    - reference_id: PMID:10772794
      supporting_text: We conclude that PKA is a major activator of discoidin expression
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:12204259
  qualifier: involved_in
  review:
    summary: PKA activation during culmination induces expression of the MADS-box transcription
      factor SrfA, linking PKA to activation of late (spore) gene expression.
    action: KEEP_AS_NON_CORE
    reason: Supports a positive regulatory role in sporulation gene expression; downstream
      of the core function.
    supported_by:
    - reference_id: PMID:12204259
      supporting_text: PKA activation during culmination leads to the induction of
        the expression of srfA
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:28057864
  qualifier: involved_in
  review:
    summary: PKA activation induces stalk-gene expression and can bypass the c-di-GMP
      requirement for stalk gene expression at the organizer.
    action: KEEP_AS_NON_CORE
    reason: Positive regulation of stalk gene expression is a downstream developmental
      role of PKA.
    supported_by:
    - reference_id: PMID:28057864
      supporting_text: PKA activation bypassed the c-di-GMP requirement for stalk gene
        expression
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:7556891
  qualifier: involved_in
  review:
    summary: The PKA catalytic subunit is required for synthesis of the PDI (phosphodiesterase
      inhibitor) transcript among early developmental genes.
    action: KEEP_AS_NON_CORE
    reason: Required for expression of a specific early gene; a downstream regulatory
      role.
    supported_by:
    - reference_id: PMID:7556891
      supporting_text: PKAcat is required for synthesis of the PDI transcript
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:23473502
  qualifier: involved_in
  review:
    summary: pkaC-null cells show prolonged/elevated expression of the extracellular
      phosphodiesterase gene pdsA, indicating PKA-dependent suppression of pdsA at
      high intracellular cAMP.
    action: KEEP_AS_NON_CORE
    reason: Supports a negative regulatory role in developmental gene expression, downstream
      of the core kinase function.
    supported_by:
    - reference_id: PMID:23473502
      supporting_text: PKA-dependent suppression of pdsA
- term:
    id: GO:0061939
    label: c-di-GMP signaling
  evidence_type: IMP
  original_reference_id: PMID:28057864
  qualifier: involved_in
  review:
    summary: c-di-GMP-induced stalk formation is transduced through ACA-produced cAMP
      acting on PKA; PKA is the terminal effector of the c-di-GMP stalk-induction pathway
      at the organizer.
    action: KEEP_AS_NON_CORE
    reason: PKA is a required downstream effector in c-di-GMP signaling; a downstream
      process role.
    supported_by:
    - reference_id: PMID:28057864
      supporting_text: DgcA activates tip-expressed ACA, which then acts on PKA to
        induce stalk genes
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IGI
  original_reference_id: PMID:21602484
  qualifier: involved_in
  review:
    summary: PKA is activated (via adenylyl cyclase ACG) in the MPBD/SDF-1 signaling
      cascade that coordinates terminal differentiation. The term is very general.
    action: KEEP_AS_NON_CORE
    reason: Correct but broad; captured more specifically by PKA's roles in cAMP/development
      signaling annotated elsewhere.
    supported_by:
    - reference_id: PMID:21602484
      supporting_text: SDF-1 apparently acts through the adenylyl cyclase ACG to activate
        the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger the production
        of more SDF-1
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:26485773
  qualifier: enables
  review:
    summary: The purified catalytic subunit possesses cAMP-dependent catalytic activity
      that is inhibited by the regulatory subunit, directly establishing the core molecular
      function.
    action: ACCEPT
    reason: Direct biochemical demonstration of the core catalytic activity.
    supported_by:
    - reference_id: PMID:26485773
      supporting_text: both the catalytic activity and its ability to be inhibited
        by addition of regulatory subunit are increased very strongly
- term:
    id: GO:0005952
    label: cAMP-dependent protein kinase complex
  evidence_type: IDA
  original_reference_id: PMID:26485773
  qualifier: is_active_in
  review:
    summary: The catalytic subunit functions within the PKA holoenzyme complex, from
      which it is released upon cAMP binding.
    action: ACCEPT
    reason: Core complex annotation directly supported by holoenzyme reconstitution.
    supported_by:
    - reference_id: PMID:26485773
      supporting_text: The CAMP-dependent holoenzyme is a dimer consisting of one regulatory
        and one catalytic subunit
- term:
    id: GO:0034237
    label: protein kinase A regulatory subunit binding
  evidence_type: IPI
  original_reference_id: PMID:26485773
  qualifier: enables
  review:
    summary: The catalytic subunit physically associates with the PKA regulatory subunit,
      an interaction that inhibits catalytic activity and is relieved by cAMP. This
      is an informative molecular function.
    action: ACCEPT
    reason: Directly demonstrated R-C interaction; a specific, informative MF (preferable
      to bare protein binding) central to cAMP-gated regulation of PKA.
    supported_by:
    - reference_id: PMID:26485773
      supporting_text: both the catalytic activity and its ability to be inhibited
        by addition of regulatory subunit are increased very strongly
- term:
    id: GO:1904643
    label: response to curcumin
  evidence_type: IMP
  original_reference_id: PMID:29135990
  qualifier: acts_upstream_of_or_within
  review:
    summary: The transcriptional and reactive-oxygen-species response to curcumin is
      PKA-dependent, including PKA-dependent downregulation of catalase A and superoxide
      dismutases.
    action: KEEP_AS_NON_CORE
    reason: A genuine but specialized downstream physiological role; not a core function.
    supported_by:
    - reference_id: PMID:29135990
      supporting_text: This transcriptionally regulated physiological response is mediated,
        in part, by the cyclic AMP-dependent protein kinase A (PKA)
- term:
    id: GO:1905301
    label: regulation of macropinocytosis
  evidence_type: IMP
  original_reference_id: PMID:29440238
  qualifier: acts_upstream_of_or_within
  review:
    summary: PKA signaling shuts down macropinocytosis at the growth-to-development
      transition; macropinocytosis continues at a high rate in PKA catalytic subunit
      mutants.
    action: KEEP_AS_NON_CORE
    reason: A real regulatory role in the growth-to-development switch, downstream
      of the core kinase function.
    supported_by:
    - reference_id: PMID:29440238
      supporting_text: macropinocytosis continues at a high rate in mutants of the
        PKA catalytic subunit
- term:
    id: GO:0031285
    label: regulation of sorocarp stalk cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:28057864
  qualifier: acts_upstream_of_or_within
  review:
    summary: PKA activity in prestalk cells is required for and can drive stalk-gene
      induction at the organizer; knockdown of PKA reduces c-di-GMP-induced stalk gene
      expression.
    action: KEEP_AS_NON_CORE
    reason: PKA regulates stalk cell differentiation, a key developmental role that
      is downstream of the core molecular function.
    supported_by:
    - reference_id: PMID:28057864
      supporting_text: knockdown of cAMP-dependent protein kinase (PKA) activity in
        prestalk cells reduced stalk gene induction by
- term:
    id: GO:0031285
    label: regulation of sorocarp stalk cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:8275851
  qualifier: acts_upstream_of_or_within
  review:
    summary: Constitutive PKA activity in prestalk cells (via cell-type-specific promoters)
      alters stalk/prestalk differentiation and morphogenesis, showing PKA regulates
      prestalk/stalk differentiation.
    action: KEEP_AS_NON_CORE
    reason: Supports a differential regulatory role of PKA in prestalk/stalk differentiation;
      downstream of the core function.
    supported_by:
    - reference_id: PMID:8275851
      supporting_text: cAMP-dependent protein kinase (PKA) activity is essential for
        aggregation, induction of prespore gene expression and multicellular development
- term:
    id: GO:1901261
    label: regulation of sorocarp spore cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:8275851
  qualifier: acts_upstream_of_or_within
  review:
    summary: Constitutive PKA activity from a prespore promoter accelerates spore cell
      differentiation, demonstrating PKA regulation of prespore/spore differentiation.
    action: KEEP_AS_NON_CORE
    reason: A central developmental regulatory role of PKA, downstream of the core
      kinase function.
    supported_by:
    - reference_id: PMID:8275851
      supporting_text: Expression of PKAcat from the prespore promoter resulted in
        abnormal morphogenesis and accelerated spore cell differentiation
- term:
    id: GO:0044671
    label: sorocarp spore cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:9373946
  qualifier: acts_upstream_of_or_within
  review:
    summary: Overexpression of the PKA catalytic subunit renders cells sporogenous
      and drives spore differentiation; spore differentiation requires PKA catalytic
      subunit activation.
    action: KEEP_AS_NON_CORE
    reason: PKA activity is a key inducer of spore cell differentiation, a core developmental
      role downstream of the catalytic function.
    supported_by:
    - reference_id: PMID:9373946
      supporting_text: overexpression of the catalytic subunit of the cAMP dependent
        protein kinase (PKA), not only renders the cells sporogenous
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8373760
  qualifier: enables
  review:
    summary: The interacting partner (UniProtKB:P05987) is the PKA regulatory subunit;
      the catalytic subunit is physically associated with the regulatory subunit. The
      more informative MF term protein kinase A regulatory subunit binding should be
      used instead of bare protein binding.
    action: MODIFY
    reason: Bare protein binding is uninformative; the documented interaction is specifically
      with the PKA regulatory subunit, so GO:0034237 better represents the function.
    proposed_replacement_terms:
    - id: GO:0034237
      label: protein kinase A regulatory subunit binding
    supported_by:
    - reference_id: PMID:8373760
      supporting_text: It is physically associated with the regulatory subunit
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IMP
  original_reference_id: PMID:1332055
  qualifier: enables
  review:
    summary: DdPK3 (pkaC) null cells lack PKA-specific kinase activity, and recombinant
      DdPK3 has PKA activity inhibitable by protein kinase inhibitor, establishing
      pkaC as the PKA catalytic subunit.
    action: ACCEPT
    reason: Genetic and biochemical evidence directly assigns the core catalytic activity
      to pkaC.
    supported_by:
    - reference_id: PMID:1332055
      supporting_text: DdPK3 null cells lack kinase activity that phosphorylates a
        PKA-specific substrate and is specifically inhibitable by recombinant cAMP-dependent
        protein kinase inhibitor
- term:
    id: GO:1904643
    label: response to curcumin
  evidence_type: IDA
  original_reference_id: PMID:26449461
  qualifier: involved_in
  review:
    summary: The cached abstract for this reference concerns curcumin effects on YakA
      signaling and GST function and does not mention PKA/pkaC, so the specific supporting
      evidence for a pkaC role in the curcumin response cannot be verified from the
      available text.
    action: UNDECIDED
    reason: Unable to verify the pkaC-specific evidence from the abstract-only cached
      publication; a PKA-dependent curcumin response is separately documented (PMID:29135990),
      but the support for this particular IDA annotation cannot be confirmed here.
- term:
    id: GO:0031154
    label: culmination involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:8565818
  qualifier: acts_upstream_of_or_within
  review:
    summary: Expression of the PKA catalytic subunit under cell-type-specific promoters
      causes ectopic terminal differentiation, and PKA is a key trigger of culmination/terminal
      differentiation.
    action: ACCEPT
    reason: PKA-driven terminal differentiation at culmination is a defining developmental
      function of pkaC, directly demonstrated.
    supported_by:
    - reference_id: PMID:8565818
      supporting_text: Expression of the catalytic (C) subunit of the cAMP-dependent
        protein kinase (PKA) of Dictyostelium under the control of heterologous, cell-type-specific
        promoters causes ectopic terminal differentiation
- term:
    id: GO:0031288
    label: sorocarp morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:8565818
  qualifier: acts_upstream_of_or_within
  review:
    summary: Manipulating PKA catalytic subunit activity produces aberrant fruiting-body
      morphogenesis, indicating a role in sorocarp morphogenesis.
    action: KEEP_AS_NON_CORE
    reason: A genuine morphogenetic consequence of PKA activity, downstream of the
      core kinase function.
    supported_by:
    - reference_id: PMID:8565818
      supporting_text: highly aberrant fruiting bodies that contain a basal mass of
        spore cells surrounding a central stalk-like structure
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:7713325
  qualifier: involved_in
  review:
    summary: PKA is a positive regulator of spore coat (cot) gene transcription; a
      dominant PKA inhibitor in prespore cells reduces cotB/cotC transcription.
    action: KEEP_AS_NON_CORE
    reason: Positive regulation of spore coat gene transcription is a real developmental
      role, downstream of the core function.
    supported_by:
    - reference_id: PMID:7713325
      supporting_text: expression of a dominant inhibitor of the cAMP dependent protein
        kinase (PKA) in prespore cells greatly reduces the transcription rates of the
        cotB and cotC genes
- term:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  evidence_type: IMP
  original_reference_id: PMID:1330484
  qualifier: enables
  review:
    summary: Overexpression of the pkaC gene (Dd PK2) raises cellular PKA (cAPK) activity
      about four-fold, confirming pkaC encodes catalytic activity.
    action: ACCEPT
    reason: Overexpression-dependent increase in PKA activity supports the core catalytic
      function.
    supported_by:
    - reference_id: PMID:1330484
      supporting_text: K-cells have about four times more protein kinase A (cAPK) activity
        than wild-type cells
- term:
    id: GO:0031285
    label: regulation of sorocarp stalk cell differentiation
  evidence_type: IGI
  original_reference_id: PMID:12455979
  qualifier: acts_upstream_of_or_within
  review:
    summary: Genetic interaction with culB shows PkaC promotes prestalk/stalk cell
      differentiation while CulB suppresses it; activating PKA (pkaR loss or pkaC overexpression)
      enhances the culB stalk phenotype.
    action: KEEP_AS_NON_CORE
    reason: Supports a regulatory role of PKA in stalk cell differentiation, downstream
      of the core kinase function.
    supported_by:
    - reference_id: PMID:12455979
      supporting_text: PkaC promotes prestalk cell differentiation, while CulB suppresses
        it
- term:
    id: GO:0030435
    label: sporulation resulting in formation of a cellular spore
  evidence_type: IMP
  original_reference_id: PMID:14680693
  qualifier: acts_upstream_of_or_within
  review:
    summary: Spore differentiation initiates with rapid encapsulation of prespore cells
      under the control of PKA; constitutive PKA activity drives precocious viable
      spore formation.
    action: KEEP_AS_NON_CORE
    reason: PKA controls the spore encapsulation/maturation step of sporulation, a
      core developmental role downstream of the catalytic function.
    supported_by:
    - reference_id: PMID:14680693
      supporting_text: Differentiation of Dictyostelium spores initiates with rapid
        encapsulation of prespore cells under the control of cAMP-dependent protein
        kinase (PKA)
- term:
    id: GO:0042173
    label: regulation of sporulation resulting in formation of a cellular spore
  evidence_type: IMP
  original_reference_id: PMID:14680693
  qualifier: acts_upstream_of_or_within
  review:
    summary: Constitutive PKA activation induces precocious formation of viable spores,
      demonstrating PKA regulation of sporulation.
    action: KEEP_AS_NON_CORE
    reason: A regulatory role in sporulation timing, downstream of the core kinase
      function.
    supported_by:
    - reference_id: PMID:14680693
      supporting_text: Constitutive activation of PKA induces precocious formation
        of viable spores in development
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: located_in
  review:
    summary: Cytosolic localization asserted in a chemoattractant-signaling review.
      Consistent with the released catalytic subunit acting as a soluble kinase.
    action: ACCEPT
    reason: Cytosol is an accepted site of action for the active catalytic subunit
      and is corroborated by the IBA cytosol annotation; a location rather than the
      core function.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: TAS
  original_reference_id: PMID:15548420
  qualifier: located_in
  review:
    summary: Centrosome localization is asserted via a review of the Dictyostelium
      centrosome. The cached abstract does not mention PKA/pkaC, so the specific supporting
      statement cannot be verified from the available text, though PKA is known to
      associate with centrosomes in other systems.
    action: UNDECIDED
    reason: Cannot verify the pkaC-specific centrosome localization from the abstract-only
      cached review; flagged as undecided pending access to the supporting full text.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:10772794
  title: Role of cAMP-dependent protein kinase during growth and early development
    of Dictyostelium discoideum.
  findings:
  - statement: PKA is a major activator of discoidin gene expression during growth
      and the growth-to-development transition.
    supporting_text: We conclude that PKA is a major activator of discoidin expression
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; pkaC-null cells show reduced discoidin expression,
      supporting a positive gene-regulatory role for PKA.
- id: PMID:11270120
  title: Interaction of gdt1 and protein kinase A (PKA) in the growth-differentiation-transition
    in Dictyostelium.
  findings:
  - statement: PKA efficiently phosphorylates a serine site of the gdt1 protein in
      vitro.
    supporting_text: found that one of them is efficiently phosphorylated by PKA in
      vitro
- id: PMID:12204259
  title: Regulated expression of the MADS-box transcription factor SrfA mediates activation
    of gene expression by protein kinase A during Dictyostelium sporulation.
  findings:
  - statement: PKA activation during culmination induces srfA expression, linking PKA
      to late (spore) gene expression.
    supporting_text: PKA activation during culmination leads to the induction of the
      expression of srfA
- id: PMID:12392578
  title: Galpha3 and protein kinase A represent cross-talking pathways for gene expression
    in Dictyostelium discoideum.
  findings:
  - statement: PKA activity was measured directly by phosphorylation of the PKA-specific
      substrate Kemptide.
    supporting_text: PKA activity, measured by phosphorylation of the PKA-specific
      substrate Kemptide
- id: PMID:12455979
  title: CulB, a putative ubiquitin ligase subunit, regulates prestalk cell differentiation
    and morphogenesis in Dictyostelium spp.
  findings:
  - statement: PkaC promotes prestalk cell differentiation whereas CulB suppresses
      it.
    supporting_text: PkaC promotes prestalk cell differentiation, while CulB suppresses
      it
- id: PMID:1330484
  title: Overexpression of Dd PK2 protein kinase causes rapid development and affects
    the intracellular cAMP pathway of Dictyostelium discoideum.
  findings:
  - statement: Overexpression of pkaC (Dd PK2) increases cellular PKA activity ~4-fold.
    supporting_text: K-cells have about four times more protein kinase A (cAPK) activity
      than wild-type cells
- id: PMID:1332055
  title: DdPK3, which plays essential roles during Dictyostelium development, encodes
    the catalytic subunit of cAMP-dependent protein kinase.
  findings:
  - statement: pkaC (DdPK3) encodes the PKA catalytic subunit; null cells lack PKA-specific
      kinase activity.
    supporting_text: DdPK3 null cells lack kinase activity that phosphorylates a PKA-specific
      substrate and is specifically inhibitable by recombinant cAMP-dependent protein
      kinase inhibitor
  - statement: Properly regulated PKA activity is essential for culmination.
    supporting_text: properly regulated PKA activity is essential for culmination
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; definitive genetic/biochemical assignment of pkaC
      as the PKA catalytic subunit and its requirement for culmination.
- id: PMID:14680693
  title: Hypertonic signal promotes stability of Dictyostelium spores via a PKA-independent
    pathway.
  findings:
  - statement: Spore differentiation initiates with PKA-controlled rapid encapsulation
      of prespore cells.
    supporting_text: Differentiation of Dictyostelium spores initiates with rapid encapsulation
      of prespore cells under the control of cAMP-dependent protein kinase (PKA)
- id: PMID:15473840
  title: Chemoattractant signaling in dictyostelium discoideum.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Review of Dictyostelium chemoattractant signaling; cited for cytosolic
      localization (TAS). Abstract does not itself detail pkaC localization.
- id: PMID:15548420
  title: Molecular and functional analysis of the dictyostelium centrosome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Centrosome review cited (TAS) for centrosome localization; the cached
      abstract does not mention PKA/pkaC, so the localization claim is unverified here.
- id: PMID:21534947
  title: STAT signaling in Dictyostelium development.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: A review focused on Dd-STAT proteins; the cached abstract does not
      establish a pkaC-specific culmination role. Culmination dependence on PKA is
      instead well supported by PMID:1332055 and PMID:8565818.
- id: PMID:21602484
  title: The polyketide MPBD initiates the SDF-1 signaling cascade that coordinates
    terminal differentiation in Dictyostelium.
  findings:
  - statement: SDF-1 signaling activates PKA via the adenylyl cyclase ACG to trigger
      further SDF-1 production during terminal differentiation.
    supporting_text: SDF-1 apparently acts through the adenylyl cyclase ACG to activate
      the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger the production
      of more SDF-1
- id: PMID:23473502
  title: 'Robustness of self-organizing chemoattractant field arising from precise
    pulse induction of its breakdown enzyme: a single-cell level analysis of PDE expression
    in Dictyostelium.'
  findings:
  - statement: PKA-dependent suppression of the extracellular phosphodiesterase gene
      pdsA contributes to its regulation.
    supporting_text: PKA-dependent suppression of pdsA
- id: PMID:26449461
  title: 'Curcumin inhibits development and cell adhesion in Dictyostelium discoideum:
    Implications for YakA signaling and GST enzyme function.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Cached abstract concerns curcumin effects on YakA/GST and does not
      mention PKA/pkaC; the pkaC 'response to curcumin' IDA annotation cannot be verified
      from this text.
- id: PMID:26485773
  title: An unusual adenosine cyclic 3',5'-phosphate-dependent protein kinase from
    Dictyostelium discoideum.
  findings:
  - statement: The Dictyostelium PKA holoenzyme is a dimer of one regulatory and one
      catalytic subunit that dissociates on cAMP binding.
    supporting_text: The CAMP-dependent holoenzyme is a dimer consisting of one regulatory
      and one catalytic subunit
  - statement: Catalytic activity and its inhibition by the regulatory subunit are
      pH-dependent.
    supporting_text: both the catalytic activity and its ability to be inhibited by
      addition of regulatory subunit are increased very strongly
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified biochemical characterization (de Gunzburg et al.
      1984) of the R-C holoenzyme; supports the complex and catalytic/regulatory-binding
      annotations.
- id: PMID:28057864
  title: Adenylate cyclase A acting on PKA mediates induction of stalk formation by
    cyclic diguanylate at the Dictyostelium organizer.
  findings:
  - statement: c-di-GMP induces stalk genes via ACA-produced cAMP acting on PKA; PKA
      activation bypasses the c-di-GMP requirement.
    supporting_text: PKA activation bypassed the c-di-GMP requirement for stalk gene
      expression
  - statement: DgcA activates tip-expressed ACA, which then acts on PKA to induce stalk
      genes.
    supporting_text: DgcA activates tip-expressed ACA, which then acts on PKA to induce
      stalk genes
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; places PKA as the terminal effector of the c-di-GMP/ACA
      stalk-induction pathway at the organizer.
- id: PMID:28302905
  title: Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to
    the chemoattractant cAMP in Dictyostelium.
  findings:
  - statement: Cells lacking PKA have severe cAMP chemotaxis defects with impaired
      directional sensing.
    supporting_text: cells lacking PKA display severe chemotaxis defects, including
      impaired directional sensing
  - statement: PKA controls chemoattractant signal transduction in part through regulation
      of RasG, Rap1 and TORC2.
    supporting_text: PKA controls chemoattractant signal transduction, in part, through
      the regulation of RasG, Rap1 and TORC2
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; full text available. Establishes PKA's role in spatiotemporal
      control of chemotactic signaling via Ras/Rap1/TORC2.
- id: PMID:29135990
  title: Curcumin affects gene expression and reactive oxygen species via a PKA dependent
    mechanism in Dictyostelium discoideum.
  findings:
  - statement: The curcumin-induced transcriptional/ROS response is mediated in part
      by PKA.
    supporting_text: This transcriptionally regulated physiological response is mediated,
      in part, by the cyclic AMP-dependent protein kinase A (PKA)
- id: PMID:29440238
  title: The physiological regulation of macropinocytosis during Dictyostelium growth
    and development.
  findings:
  - statement: Macropinocytosis is shut down by PKA signaling; it persists at a high
      rate in PKA catalytic subunit mutants.
    supporting_text: macropinocytosis continues at a high rate in mutants of the PKA
      catalytic subunit
- id: PMID:29704004
  title: The transcription factor Spores Absent A is a PKA dependent inducer of Dictyostelium
    sporulation.
  findings:
  - statement: SpaA-dependent spore gene expression requires PKA and is stimulated
      by the PKA agonist 8Br-cAMP.
    supporting_text: SpaA dependent spore gene expression required PKA in vivo and
      was stimulated in vitro by the membrane-permeant PKA agonist 8Br-cAMP
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; full text available. Places PKA upstream of the
      SpaA transcription factor in the sporulation gene-expression pathway.
- id: PMID:30462573
  title: An endogenous chemorepellent directs cell movement by inhibiting pseudopods
    at one side of cells.
  findings:
  - statement: AprA chemorepulsion uses a subset of cAMP chemoattraction pathways including
      protein kinase A.
    supporting_text: AprA uses a subset of chemoattraction signal transduction pathways
      including Ras, protein kinase A, target of rapamycin (TOR), phospholipase A,
      and ERK1
- id: PMID:7556891
  title: Regulation of Dictyostelium early development genes in signal transduction
    mutants.
  findings:
  - statement: The PKA catalytic subunit is required for synthesis of the PDI transcript.
    supporting_text: PKAcat is required for synthesis of the PDI transcript
- id: PMID:7713325
  title: Protein kinase A is a positive regulator of spore coat gene transcription
    in Dictyostelium.
  findings:
  - statement: A dominant PKA inhibitor in prespore cells greatly reduces cotB and
      cotC transcription.
    supporting_text: expression of a dominant inhibitor of the cAMP dependent protein
      kinase (PKA) in prespore cells greatly reduces the transcription rates of the
      cotB and cotC genes
- id: PMID:8275851
  title: cAMP-dependent protein kinase differentially regulates prestalk and prespore
    differentiation during Dictyostelium development.
  findings:
  - statement: PKA activity is essential for aggregation, prespore gene induction and
      multicellular development.
    supporting_text: cAMP-dependent protein kinase (PKA) activity is essential for
      aggregation, induction of prespore gene expression and multicellular development
  - statement: Constitutive PKA from a prespore promoter accelerates spore cell differentiation.
    supporting_text: Expression of PKAcat from the prespore promoter resulted in abnormal
      morphogenesis and accelerated spore cell differentiation
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; demonstrates differential PKA control of prestalk
      versus prespore differentiation.
- id: PMID:8373760
  title: An unusual catalytic subunit for the cAMP-dependent protein kinase of Dictyostelium
    discoideum.
  findings:
  - statement: PkaC is the ~73 kDa catalytic subunit that copurifies with cAPK activity
      and associates with the regulatory subunit.
    supporting_text: PkaC copurifies with cAPK activity
  - statement: PkaC is physically associated with the regulatory subunit.
    supporting_text: It is physically associated with the regulatory subunit
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; identifies the unusually large PkaC as the catalytic
      subunit and documents R-C association.
- id: PMID:8565818
  title: Induction of terminal differentiation of Dictyostelium by cAMP-dependent protein
    kinase and opposing effects of intracellulr and extracellular cAMP on stalk cell
    differentiation.
  findings:
  - statement: Cell-type-specific expression of the PKA catalytic subunit causes ectopic
      terminal differentiation.
    supporting_text: Expression of the catalytic (C) subunit of the cAMP-dependent
      protein kinase (PKA) of Dictyostelium under the control of heterologous, cell-type-specific
      promoters causes ectopic terminal differentiation
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; PKA is sufficient to drive terminal (spore/stalk)
      differentiation.
- id: PMID:8670837
  title: Dual role of cAMP and involvement of both G-proteins and ras in regulation
    of ERK2 in Dictyostelium discoideum.
  findings:
  - statement: Intracellular cAMP and PKA are essential for adaptation of the ERK2
      response.
    supporting_text: Intracellular cAMP and cAMP-dependent protein kinase (PKA) are
      essential for adaptation of the ERK2 response
- id: PMID:9020088
  title: The Dictyostelium mitogen-activated protein kinase ERK2 is regulated by Ras
    and cAMP-dependent protein kinase (PKA) and mediates PKA function.
  findings:
  - statement: PKA is an important regulator of ERK2 activation and adaptation.
    supporting_text: Ras and cAMP-dependent protein kinase (PKA), are important regulators
      of ERK2 activation and adaptation
- id: PMID:9373946
  title: A new spore differentiation factor (SDF) secreted by Dictyostelium cells is
    phosphorylated by the cAMP dependent protein kinase.
  findings:
  - statement: Overexpression of the PKA catalytic subunit renders cells sporogenous.
    supporting_text: overexpression of the catalytic subunit of the cAMP dependent
      protein kinase (PKA), not only renders the cells sporogenous
- id: PMID:9843585
  title: A molecular network that produces spontaneous oscillations in excitable cells
    of Dictyostelium.
  findings:
  - statement: In the cAMP oscillator, a rise in internal cAMP activates PKA, which
      inhibits ERK2 and causes loss of CAR1 ligand binding.
    supporting_text: A rise in the internal concentration of cAMP activates protein
      kinase A such that it inhibits ERK2 and leads to a loss-of-ligand binding by
      CAR1
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; models PKA as an essential negative-feedback node
      of the cAMP-relay oscillator.
core_functions:
- description: Catalytic subunit of cAMP-dependent protein kinase (PKA). As an AGC-family
    Ser/Thr protein kinase, pkaC phosphorylates serine/threonine residues on target
    proteins using ATP, and this catalytic activity is the principal intracellular
    effector of cAMP that drives the Dictyostelium developmental program (aggregation,
    prespore/prestalk gene expression, culmination and terminal spore/stalk maturation).
  molecular_function:
    id: GO:0004691
    label: cAMP-dependent protein kinase activity
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0005952
    label: cAMP-dependent protein kinase complex
  supported_by:
  - reference_id: PMID:1332055
    supporting_text: DdPK3 null cells lack kinase activity that phosphorylates a PKA-specific
      substrate and is specifically inhibitable by recombinant cAMP-dependent protein
      kinase inhibitor
  - reference_id: PMID:8373760
    supporting_text: PkaC copurifies with cAPK activity
- description: Binds the PKA regulatory (R) subunit to form the inactive holoenzyme;
    this cAMP-gated interaction keeps catalytic activity repressed until cAMP binds
    the R subunit and releases the active catalytic subunit. This regulatory-subunit
    binding is central to how rising intracellular cAMP is transduced into PKA activity.
  molecular_function:
    id: GO:0034237
    label: protein kinase A regulatory subunit binding
  in_complex:
    id: GO:0005952
    label: cAMP-dependent protein kinase complex
  supported_by:
  - reference_id: PMID:26485773
    supporting_text: The CAMP-dependent holoenzyme is a dimer consisting of one regulatory
      and one catalytic subunit
  - reference_id: PMID:8373760
    supporting_text: It is physically associated with the regulatory subunit