pkaC

UniProt ID: P34099
Organism: Dictyostelium discoideum
Review Status: COMPLETE
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Gene 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 Review

GO Term Evidence Action Reason
GO:0005829 cytosol
IBA
GO_REF:0000033
ACCEPT
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.
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.
Supporting Evidence:
PMID:26485773
the rest is recovered in the form of dissociated regulatory and catalytic subunits that were purified
GO:0005952 cAMP-dependent protein kinase complex
IBA
GO_REF:0000033
ACCEPT
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.
Reason: Directly established biochemically for the Dictyostelium enzyme; the holoenzyme is an R-C dimer, and cAMP releases the active C subunit.
Supporting Evidence:
PMID:26485773
The CAMP-dependent holoenzyme is a dimer consisting of one regulatory and one catalytic subunit
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
IBA
GO_REF:0000033
KEEP AS NON CORE
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).
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.
Supporting Evidence:
PMID:9843585
A rise in the internal concentration of cAMP activates protein kinase A
GO:0004691 cAMP-dependent protein kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: cAMP-dependent protein kinase activity is the defining, experimentally established molecular function of pkaC and is broadly supported across orthologs.
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.
Supporting Evidence:
PMID:8373760
PkaC copurifies with cAPK activity
GO:0004672 protein kinase activity
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: InterPro-based general protein kinase activity. Correct but less informative than the specific cAMP-dependent protein kinase activity term.
Reason: Accurate parent term derived from the protein kinase domain, but the specific child GO:0004691 better captures the core function.
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: InterPro-based Ser/Thr kinase activity. Correct but general relative to cAMP-dependent protein kinase activity.
Reason: PKA is a Ser/Thr kinase, so this is accurate; the specific term GO:0004691 is preferred for the core function.
GO:0004691 cAMP-dependent protein kinase activity
IEA
GO_REF:0000003
ACCEPT
Summary: EC 2.7.11.11 mapping to cAMP-dependent protein kinase activity, matching the UniProt catalytic activity annotation.
Reason: Electronic assignment that correctly recapitulates the core molecular function.
GO:0005524 ATP binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: ATP binding inferred from the protein kinase ATP-binding site. A required substrate-binding property supporting catalysis.
Reason: ATP binding is a correct, mechanistically necessary property of the kinase but is subordinate to the catalytic activity that defines the function.
GO:0009653 anatomical structure morphogenesis
IEA
GO_REF:0000117
KEEP AS NON CORE
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.
Reason: Correct at a high level given PKA's developmental role, but too general; the specific GO:0031288 sorocarp morphogenesis annotation is preferred.
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116
KEEP AS NON CORE
Summary: Rhea/reaction-based protein serine kinase activity, consistent with the Ser-phosphorylation reaction annotated in UniProt.
Reason: Accurate reaction-derived MF; the specific cAMP-dependent protein kinase activity term captures the core function.
GO:0031154 culmination involved in sorocarp development
IDA
PMID:21534947
STAT signaling in Dictyostelium development.
ACCEPT
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.
Reason: Culmination dependence on PKA is well established experimentally; the catalytic subrole in triggering terminal differentiation at culmination is a defining developmental function.
Supporting Evidence:
PMID:1332055
properly regulated PKA activity is essential for culmination
GO:0140676 oscillatory cAMP signaling
IDA
PMID:9843585
A molecular network that produces spontaneous oscillations i...
KEEP AS NON CORE
Summary: PKA is an essential negative-feedback element of the cAMP-relay oscillator network, inhibiting ERK2 and CAR1 ligand binding once internal cAMP rises.
Reason: PKA is required for the oscillatory network, but this is a downstream systems-level process rather than the core molecular function.
Supporting Evidence:
PMID:9843585
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
GO:0007264 small GTPase-mediated signal transduction
IMP
PMID:28302905
Protein kinase A regulates the Ras, Rap1 and TORC2 pathways ...
KEEP AS NON CORE
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.
Reason: PKA acts upstream of RasG/Rap1 signaling during chemotaxis; this is a downstream regulatory role rather than the core kinase function.
Supporting Evidence:
PMID:28302905
PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1 and TORC2
GO:0004691 cAMP-dependent protein kinase activity
IDA
PMID:12392578
Galpha3 and protein kinase A represent cross-talking pathway...
ACCEPT
Summary: PKA activity directly measured by phosphorylation of the PKA-specific substrate Kemptide, confirming the core catalytic function.
Reason: Direct biochemical measurement of PKA catalytic activity supports the core molecular function.
Supporting Evidence:
PMID:12392578
PKA activity, measured by phosphorylation of the PKA-specific substrate Kemptide
GO:0140986 G protein-coupled chemorepellent receptor signaling pathway
IMP
PMID:30462573
An endogenous chemorepellent directs cell movement by inhibi...
KEEP AS NON CORE
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.
Reason: PKA is a required component of the chemorepellent signaling pathway, but this is a downstream biological process, not the core molecular function.
Supporting Evidence:
PMID:30462573
AprA uses a subset of chemoattraction signal transduction pathways including Ras, protein kinase A, target of rapamycin (TOR), phospholipase A, and ERK1
GO:0043327 chemotaxis to cAMP
IMP
PMID:28302905
Protein kinase A regulates the Ras, Rap1 and TORC2 pathways ...
KEEP AS NON CORE
Summary: Cells lacking PKA display severe cAMP chemotaxis defects including impaired directional sensing, establishing a required role for PKA in cAMP chemotaxis.
Reason: PKA is essential for cAMP chemotaxis, but this behavioral process is downstream of PKA's core catalytic function.
Supporting Evidence:
PMID:28302905
cells lacking PKA display severe chemotaxis defects, including impaired directional sensing
GO:0071964 establishment of cell polarity regulating cell shape
IMP
PMID:28302905
Protein kinase A regulates the Ras, Rap1 and TORC2 pathways ...
KEEP AS NON CORE
Summary: PKA restricts the site and extent of chemotactic pathway activation and thereby pseudopod protrusion, contributing to cell polarity and shape during chemotaxis.
Reason: Supported by the pkaC-null chemotaxis phenotype, but this is a downstream cell-biological consequence of PKA signaling.
Supporting Evidence:
PMID:28302905
plays a key role in restricting the extent, as well as the site, of chemotactic pathway activation and, thereby, pseudopod protrusion
GO:0005524 ATP binding
IC
PMID:1330484
Overexpression of Dd PK2 protein kinase causes rapid develop...
KEEP AS NON CORE
Summary: ATP binding inferred by curators from the demonstrated cAMP-dependent protein kinase activity. A mechanistically required property.
Reason: Correct inference from kinase activity; subordinate to the core catalytic function.
GO:0019887 protein kinase regulator activity
IDA
PMID:28302905
Protein kinase A regulates the Ras, Rap1 and TORC2 pathways ...
MARK AS OVER ANNOTATED
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.
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.
Supporting Evidence:
PMID:28302905
PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1 and TORC2
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
IMP
PMID:28302905
Protein kinase A regulates the Ras, Rap1 and TORC2 pathways ...
KEEP AS NON CORE
Summary: Dictyostelium-specific cAMP chemoattractant receptor signaling pathway term; PKA is a required, spatiotemporally regulating component of cAR1/ACA-driven cAMP signaling.
Reason: Well supported by the pkaC-null phenotype, but this is a downstream signaling pathway rather than the core molecular function.
Supporting Evidence:
PMID:28302905
PKA is necessary for proper spatiotemporal regulation of early chemoattractant signal transduction pathways
GO:0000165 MAPK cascade
IMP
PMID:9020088
The Dictyostelium mitogen-activated protein kinase ERK2 is r...
KEEP AS NON CORE
Summary: PKA is an important regulator of ERK2 activation and adaptation and lies downstream of ERK2 in mediating PKA function during aggregation and development.
Reason: PKA participates in the ERK2 MAPK module as a regulator, a downstream process role rather than the core catalytic function.
Supporting Evidence:
PMID:9020088
Ras and cAMP-dependent protein kinase (PKA), are important regulators of ERK2 activation and adaptation
GO:0019887 protein kinase regulator activity
IMP
PMID:9020088
The Dictyostelium mitogen-activated protein kinase ERK2 is r...
MARK AS OVER ANNOTATED
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.
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.
Supporting Evidence:
PMID:9020088
Ras and cAMP-dependent protein kinase (PKA), are important regulators of ERK2 activation and adaptation
GO:0004860 protein kinase inhibitor activity
IMP
PMID:8670837
Dual role of cAMP and involvement of both G-proteins and ras...
MARK AS OVER ANNOTATED
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.
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.
Supporting Evidence:
PMID:8670837
Intracellular cAMP and cAMP-dependent protein kinase (PKA) are essential for adaptation of the ERK2 response
GO:0106310 protein serine kinase activity
IDA
PMID:11270120
Interaction of gdt1 and protein kinase A (PKA) in the growth...
KEEP AS NON CORE
Summary: PKA directly phosphorylates a serine site in the gdt1 protein in vitro, demonstrating protein serine kinase activity on a physiological substrate.
Reason: Directly demonstrated Ser-kinase activity; accurate but the specific cAMP-dependent protein kinase activity term is preferred for the core function.
Supporting Evidence:
PMID:11270120
found that one of them is efficiently phosphorylated by PKA in vitro
GO:0005952 cAMP-dependent protein kinase complex
IDA
PMID:26485773
An unusual adenosine cyclic 3',5'-phosphate-dependent protei...
ACCEPT
Summary: Directly demonstrated that the catalytic subunit forms the PKA holoenzyme with the regulatory subunit as an R-C dimer.
Reason: Core annotation established by biochemical reconstitution of the holoenzyme from purified subunits.
Supporting Evidence:
PMID:26485773
The CAMP-dependent holoenzyme is a dimer consisting of one regulatory and one catalytic subunit
GO:0006355 regulation of DNA-templated transcription
IDA
PMID:29704004
The transcription factor Spores Absent A is a PKA dependent ...
KEEP AS NON CORE
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.
Reason: PKA regulates developmental transcription indirectly via downstream transcription factors; a real but downstream role rather than the core molecular function.
Supporting Evidence:
PMID:29704004
SpaA dependent spore gene expression required PKA in vivo and was stimulated in vitro by the membrane-permeant PKA agonist 8Br-cAMP
GO:0010628 positive regulation of gene expression
IMP
PMID:10772794
Role of cAMP-dependent protein kinase during growth and earl...
KEEP AS NON CORE
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.
Reason: Genuine positive regulatory role in developmental gene expression, but downstream of the core kinase function.
Supporting Evidence:
PMID:10772794
We conclude that PKA is a major activator of discoidin expression
GO:0010628 positive regulation of gene expression
IMP
PMID:12204259
Regulated expression of the MADS-box transcription factor Sr...
KEEP AS NON CORE
Summary: PKA activation during culmination induces expression of the MADS-box transcription factor SrfA, linking PKA to activation of late (spore) gene expression.
Reason: Supports a positive regulatory role in sporulation gene expression; downstream of the core function.
Supporting Evidence:
PMID:12204259
PKA activation during culmination leads to the induction of the expression of srfA
GO:0010628 positive regulation of gene expression
IMP
PMID:28057864
Adenylate cyclase A acting on PKA mediates induction of stal...
KEEP AS NON CORE
Summary: PKA activation induces stalk-gene expression and can bypass the c-di-GMP requirement for stalk gene expression at the organizer.
Reason: Positive regulation of stalk gene expression is a downstream developmental role of PKA.
Supporting Evidence:
PMID:28057864
PKA activation bypassed the c-di-GMP requirement for stalk gene expression
GO:0010628 positive regulation of gene expression
IMP
PMID:7556891
Regulation of Dictyostelium early development genes in signa...
KEEP AS NON CORE
Summary: The PKA catalytic subunit is required for synthesis of the PDI (phosphodiesterase inhibitor) transcript among early developmental genes.
Reason: Required for expression of a specific early gene; a downstream regulatory role.
Supporting Evidence:
PMID:7556891
PKAcat is required for synthesis of the PDI transcript
GO:0010629 negative regulation of gene expression
IMP
PMID:23473502
Robustness of self-organizing chemoattractant field arising ...
KEEP AS NON CORE
Summary: pkaC-null cells show prolonged/elevated expression of the extracellular phosphodiesterase gene pdsA, indicating PKA-dependent suppression of pdsA at high intracellular cAMP.
Reason: Supports a negative regulatory role in developmental gene expression, downstream of the core kinase function.
Supporting Evidence:
PMID:23473502
PKA-dependent suppression of pdsA
GO:0061939 c-di-GMP signaling
IMP
PMID:28057864
Adenylate cyclase A acting on PKA mediates induction of stal...
KEEP AS NON CORE
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.
Reason: PKA is a required downstream effector in c-di-GMP signaling; a downstream process role.
Supporting Evidence:
PMID:28057864
DgcA activates tip-expressed ACA, which then acts on PKA to induce stalk genes
GO:0007165 signal transduction
IGI
PMID:21602484
The polyketide MPBD initiates the SDF-1 signaling cascade th...
KEEP AS NON CORE
Summary: PKA is activated (via adenylyl cyclase ACG) in the MPBD/SDF-1 signaling cascade that coordinates terminal differentiation. The term is very general.
Reason: Correct but broad; captured more specifically by PKA's roles in cAMP/development signaling annotated elsewhere.
Supporting Evidence:
PMID:21602484
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
GO:0004691 cAMP-dependent protein kinase activity
IDA
PMID:26485773
An unusual adenosine cyclic 3',5'-phosphate-dependent protei...
ACCEPT
Summary: The purified catalytic subunit possesses cAMP-dependent catalytic activity that is inhibited by the regulatory subunit, directly establishing the core molecular function.
Reason: Direct biochemical demonstration of the core catalytic activity.
Supporting Evidence:
PMID:26485773
both the catalytic activity and its ability to be inhibited by addition of regulatory subunit are increased very strongly
GO:0005952 cAMP-dependent protein kinase complex
IDA
PMID:26485773
An unusual adenosine cyclic 3',5'-phosphate-dependent protei...
ACCEPT
Summary: The catalytic subunit functions within the PKA holoenzyme complex, from which it is released upon cAMP binding.
Reason: Core complex annotation directly supported by holoenzyme reconstitution.
Supporting Evidence:
PMID:26485773
The CAMP-dependent holoenzyme is a dimer consisting of one regulatory and one catalytic subunit
GO:0034237 protein kinase A regulatory subunit binding
IPI
PMID:26485773
An unusual adenosine cyclic 3',5'-phosphate-dependent protei...
ACCEPT
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.
Reason: Directly demonstrated R-C interaction; a specific, informative MF (preferable to bare protein binding) central to cAMP-gated regulation of PKA.
Supporting Evidence:
PMID:26485773
both the catalytic activity and its ability to be inhibited by addition of regulatory subunit are increased very strongly
GO:1904643 response to curcumin
IMP
PMID:29135990
Curcumin affects gene expression and reactive oxygen species...
KEEP AS NON CORE
Summary: The transcriptional and reactive-oxygen-species response to curcumin is PKA-dependent, including PKA-dependent downregulation of catalase A and superoxide dismutases.
Reason: A genuine but specialized downstream physiological role; not a core function.
Supporting Evidence:
PMID:29135990
This transcriptionally regulated physiological response is mediated, in part, by the cyclic AMP-dependent protein kinase A (PKA)
GO:1905301 regulation of macropinocytosis
IMP
PMID:29440238
The physiological regulation of macropinocytosis during Dict...
KEEP AS NON CORE
Summary: PKA signaling shuts down macropinocytosis at the growth-to-development transition; macropinocytosis continues at a high rate in PKA catalytic subunit mutants.
Reason: A real regulatory role in the growth-to-development switch, downstream of the core kinase function.
Supporting Evidence:
PMID:29440238
macropinocytosis continues at a high rate in mutants of the PKA catalytic subunit
GO:0031285 regulation of sorocarp stalk cell differentiation
IMP
PMID:28057864
Adenylate cyclase A acting on PKA mediates induction of stal...
KEEP AS NON CORE
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.
Reason: PKA regulates stalk cell differentiation, a key developmental role that is downstream of the core molecular function.
Supporting Evidence:
PMID:28057864
knockdown of cAMP-dependent protein kinase (PKA) activity in prestalk cells reduced stalk gene induction by
GO:0031285 regulation of sorocarp stalk cell differentiation
IMP
PMID:8275851
cAMP-dependent protein kinase differentially regulates prest...
KEEP AS NON CORE
Summary: Constitutive PKA activity in prestalk cells (via cell-type-specific promoters) alters stalk/prestalk differentiation and morphogenesis, showing PKA regulates prestalk/stalk differentiation.
Reason: Supports a differential regulatory role of PKA in prestalk/stalk differentiation; downstream of the core function.
Supporting Evidence:
PMID:8275851
cAMP-dependent protein kinase (PKA) activity is essential for aggregation, induction of prespore gene expression and multicellular development
GO:1901261 regulation of sorocarp spore cell differentiation
IMP
PMID:8275851
cAMP-dependent protein kinase differentially regulates prest...
KEEP AS NON CORE
Summary: Constitutive PKA activity from a prespore promoter accelerates spore cell differentiation, demonstrating PKA regulation of prespore/spore differentiation.
Reason: A central developmental regulatory role of PKA, downstream of the core kinase function.
Supporting Evidence:
PMID:8275851
Expression of PKAcat from the prespore promoter resulted in abnormal morphogenesis and accelerated spore cell differentiation
GO:0044671 sorocarp spore cell differentiation
IMP
PMID:9373946
A new spore differentiation factor (SDF) secreted by Dictyos...
KEEP AS NON CORE
Summary: Overexpression of the PKA catalytic subunit renders cells sporogenous and drives spore differentiation; spore differentiation requires PKA catalytic subunit activation.
Reason: PKA activity is a key inducer of spore cell differentiation, a core developmental role downstream of the catalytic function.
Supporting Evidence:
PMID:9373946
overexpression of the catalytic subunit of the cAMP dependent protein kinase (PKA), not only renders the cells sporogenous
GO:0005515 protein binding
IPI
PMID:8373760
An unusual catalytic subunit for the cAMP-dependent protein ...
MODIFY
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.
Reason: Bare protein binding is uninformative; the documented interaction is specifically with the PKA regulatory subunit, so GO:0034237 better represents the function.
Supporting Evidence:
PMID:8373760
It is physically associated with the regulatory subunit
GO:0004691 cAMP-dependent protein kinase activity
IMP
PMID:1332055
DdPK3, which plays essential roles during Dictyostelium deve...
ACCEPT
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.
Reason: Genetic and biochemical evidence directly assigns the core catalytic activity to pkaC.
Supporting Evidence:
PMID:1332055
DdPK3 null cells lack kinase activity that phosphorylates a PKA-specific substrate and is specifically inhibitable by recombinant cAMP-dependent protein kinase inhibitor
GO:1904643 response to curcumin
IDA
PMID:26449461
Curcumin inhibits development and cell adhesion in Dictyoste...
UNDECIDED
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.
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.
GO:0031154 culmination involved in sorocarp development
IMP
PMID:8565818
Induction of terminal differentiation of Dictyostelium by cA...
ACCEPT
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.
Reason: PKA-driven terminal differentiation at culmination is a defining developmental function of pkaC, directly demonstrated.
Supporting Evidence:
PMID:8565818
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
GO:0031288 sorocarp morphogenesis
IMP
PMID:8565818
Induction of terminal differentiation of Dictyostelium by cA...
KEEP AS NON CORE
Summary: Manipulating PKA catalytic subunit activity produces aberrant fruiting-body morphogenesis, indicating a role in sorocarp morphogenesis.
Reason: A genuine morphogenetic consequence of PKA activity, downstream of the core kinase function.
Supporting Evidence:
PMID:8565818
highly aberrant fruiting bodies that contain a basal mass of spore cells surrounding a central stalk-like structure
GO:0010628 positive regulation of gene expression
IDA
PMID:7713325
Protein kinase A is a positive regulator of spore coat gene ...
KEEP AS NON CORE
Summary: PKA is a positive regulator of spore coat (cot) gene transcription; a dominant PKA inhibitor in prespore cells reduces cotB/cotC transcription.
Reason: Positive regulation of spore coat gene transcription is a real developmental role, downstream of the core function.
Supporting Evidence:
PMID:7713325
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
GO:0004691 cAMP-dependent protein kinase activity
IMP
PMID:1330484
Overexpression of Dd PK2 protein kinase causes rapid develop...
ACCEPT
Summary: Overexpression of the pkaC gene (Dd PK2) raises cellular PKA (cAPK) activity about four-fold, confirming pkaC encodes catalytic activity.
Reason: Overexpression-dependent increase in PKA activity supports the core catalytic function.
Supporting Evidence:
PMID:1330484
K-cells have about four times more protein kinase A (cAPK) activity than wild-type cells
GO:0031285 regulation of sorocarp stalk cell differentiation
IGI
PMID:12455979
CulB, a putative ubiquitin ligase subunit, regulates prestal...
KEEP AS NON CORE
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.
Reason: Supports a regulatory role of PKA in stalk cell differentiation, downstream of the core kinase function.
Supporting Evidence:
PMID:12455979
PkaC promotes prestalk cell differentiation, while CulB suppresses it
GO:0030435 sporulation resulting in formation of a cellular spore
IMP
PMID:14680693
Hypertonic signal promotes stability of Dictyostelium spores...
KEEP AS NON CORE
Summary: Spore differentiation initiates with rapid encapsulation of prespore cells under the control of PKA; constitutive PKA activity drives precocious viable spore formation.
Reason: PKA controls the spore encapsulation/maturation step of sporulation, a core developmental role downstream of the catalytic function.
Supporting Evidence:
PMID:14680693
Differentiation of Dictyostelium spores initiates with rapid encapsulation of prespore cells under the control of cAMP-dependent protein kinase (PKA)
GO:0042173 regulation of sporulation resulting in formation of a cellular spore
IMP
PMID:14680693
Hypertonic signal promotes stability of Dictyostelium spores...
KEEP AS NON CORE
Summary: Constitutive PKA activation induces precocious formation of viable spores, demonstrating PKA regulation of sporulation.
Reason: A regulatory role in sporulation timing, downstream of the core kinase function.
Supporting Evidence:
PMID:14680693
Constitutive activation of PKA induces precocious formation of viable spores in development
GO:0005829 cytosol
TAS
PMID:15473840
Chemoattractant signaling in dictyostelium discoideum.
ACCEPT
Summary: Cytosolic localization asserted in a chemoattractant-signaling review. Consistent with the released catalytic subunit acting as a soluble kinase.
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.
GO:0005813 centrosome
TAS
PMID:15548420
Molecular and functional analysis of the dictyostelium centr...
UNDECIDED
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.
Reason: Cannot verify the pkaC-specific centrosome localization from the abstract-only cached review; flagged as undecided pending access to the supporting full text.

Core Functions

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).

Supporting Evidence:
  • PMID:1332055
    DdPK3 null cells lack kinase activity that phosphorylates a PKA-specific substrate and is specifically inhibitable by recombinant cAMP-dependent protein kinase inhibitor
  • PMID:8373760
    PkaC copurifies with cAPK activity

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.

Supporting Evidence:
  • PMID:26485773
    The CAMP-dependent holoenzyme is a dimer consisting of one regulatory and one catalytic subunit
  • PMID:8373760
    It is physically associated with the regulatory subunit

References

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