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.
| 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. Proposed replacements: protein kinase A regulatory subunit binding 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. |
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