BioPAX pathway converted from "cAMP Induces dissociation of active protein kinase A subunits from the PKA:Akap150:Iqgap1 complex" in the Reactome database.LEFT-TO-RIGHTcAMP Induces dissociation of active protein kinase A subunits from the PKA:Akap150:Iqgap1 complexThe regulatory subunits of protein kinase A bind cAMP which causes the catalytic subunits of protein kinase A to dissociate and become active. The regulatory subunits remain tethered at the plasma membrane by interaction with Akap5/Akap150 and Iqgap1.Authored: May, B, 2009-11-19Reviewed: May, B, 2009-11-19Edited: May, B, 2009-11-19cAMPCyclic adenylic acid3',5'-cyclic AMPCyclic AMPAdenosine 3',5'-phosphateReactome DB_ID: 30389cytosolGENE ONTOLOGYGO:00058293',5'-cyclic AMP [ChEBI:17489]3',5'-cyclic AMPChEBICHEBI:17489Reactome Database ID Release 7030389Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30389ReactomeR-ALL-303893Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30389.3Reactomehttp://www.reactome.org4PKA:Akap150,79:Iqgap1Reactome DB_ID: 446967plasma membraneGENE ONTOLOGYGO:0005886Iqgap1Reactome DB_ID: 446989Reactome Database ID Release 70446989Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446989ReactomeR-RNO-4469891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446989.11Akap5A-kinase anchor protein 5AKAP5_RATAkap5Reactome DB_ID: 446984UniProt:P24587 Akap5Akap5Akap150FUNCTION May anchor the PKA kinase to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors.SUBUNIT Interacts with ADCY8, and enhances its phosphorylation at lipid rafts (By similarity). Binds dimer of the RII-beta regulatory subunit of cAMP-dependent protein kinase.DOMAIN The N-terminal region, which is highly basic, is required for interaction with calmodulin.PTM Palmitoylation at Cys-36 and Cys-123 plays a key role in targeting to lipid rafts.Rattus norvegicusNCBI Taxonomy10116UniProtP245871EQUAL714EQUALReactome Database ID Release 70446984Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446984ReactomeR-RNO-4469841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446984.11Protein kinase A tetramer (rat)Reactome DB_ID: 446971Converted from EntitySet in ReactomeProtein Kinase A regulatory subunit (rat)Reactome DB_ID: 446981Prkar1acAMP-dependent protein kinase type I-alpha regulatory subunitKAP0_RATPrkar1aReactome DB_ID: 446986UniProt:P09456 Prkar1aPrkar1aFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.SUBUNIT The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4. Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with CBFA2T3. Interacts with PRKX; regulates this cAMP-dependent protein kinase (By similarity). Interacts with smAKAP; this interaction may target PRKAR1A to the plasma membrane. Interacts with AICDA (By similarity).PTM The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.MISCELLANEOUS Two types of regulatory chains are found: type I, which predominates in skeletal muscle, and type II, which predominates in cardiac muscle.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP094562EQUAL381EQUALReactome Database ID Release 70446986Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446986ReactomeR-RNO-4469861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446986.1Prkar1bcAMP-dependent protein kinase type I-beta regulatory subunitKAP1_RATPrkar1bReactome DB_ID: 446976UniProt:P81377 Prkar1bPrkar1bFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.SUBUNIT The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. Interacts with PRKX; regulates this cAMP-dependent protein kinase (By similarity). Interacts with smAKAP; this interaction may target PRKAR1B to the plasma membrane (By similarity).TISSUE SPECIFICITY Abundant in brain and testis. No expression in lung, heart, liver, spleen, kidney and skeletal muscle.PTM The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP813772EQUAL381EQUALReactome Database ID Release 70446976Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446976ReactomeR-RNO-4469761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446976.1Prkar2bcAMP-dependent protein kinase type II-beta regulatory subunitKAP3_RATPrkar2bReactome DB_ID: 446975UniProt:P12369 Prkar2bPrkar2bFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.SUBUNIT The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with the phosphorylated form of PJA2 (By similarity). Forms a complex composed of PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (By similarity).TISSUE SPECIFICITY Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible. Brain. Present in a few pyramidal neurons and mostly in mossy fibers. Colocalizes with PJA2 in dentate granule cells and at postsynaptic sites of primary hippocampal neurons.PTM Phosphorylated by the activated catalytic chain.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP123692EQUAL416EQUALReactome Database ID Release 70446975Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446975ReactomeR-RNO-4469751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446975.1Prkar2acAMP-dependent protein kinase type II-alpha regulatory subunitKAP2_RATPrkar2aReactome DB_ID: 446980UniProt:P12368 Prkar2aPrkar2aFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.SUBUNIT The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3 (By similarity). Interacts with the phosphorylated form of PJA2 (By similarity). Interacts with MYRIP; his interaction may link PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release. Forms a complex composed of PRKAR2A, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (By similarity). Interacts with ADCY8; inhibits adenylate cyclase activity through PKA phosphorylation (By similarity).TISSUE SPECIFICITY Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.PTM Phosphorylated by the activated catalytic chain.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP123682EQUAL401EQUALReactome Database ID Release 70446980Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446980ReactomeR-RNO-4469801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446980.1Reactome Database ID Release 70446981Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446981ReactomeR-RNO-4469811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446981.12Converted from EntitySet in ReactomeProtein kinase A catalytic subunit (rat)Reactome DB_ID: 446977PKA C-alphacAMP-dependent protein kinase, alpha-catalytic subunitReactome DB_ID: 163527UniProt:P27791 PrkacaPrkacaFUNCTION Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation (By similarity). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity).ACTIVITY REGULATION Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis.SUBUNIT A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes (By similarity). Interacts with APOBEC3G and AICDA (By similarity). Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11 (By similarity). Interacts with MROH2B (By similarity). Interacts with HSF1 (By similarity). Isoform 2 interacts with TCP11 (By similarity).TISSUE SPECIFICITY Ubiquitously expressed. Isoform 2 is round spermatid specific.DEVELOPMENTAL STAGE In spermatids, isoform 1 is expressed until spermatids become elutriated, whereafter isoform 2 is expressed.PTM Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.PTM Autophosphorylated. Phosphorylation is enhanced by vitamin K(2). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (By similarity).PTM Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.UniProtP27791Reactome Database ID Release 70163527Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=163527ReactomeR-RNO-1635271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-163527.1PKA C-betacAMP-dependent protein kinase, beta-catalytic subunitReactome DB_ID: 163504UniProt:P68182 PrkacbPrkacbPkacbFUNCTION Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates GPKOW which regulates its ability to bind RNA.ACTIVITY REGULATION Activated by cAMP.SUBUNIT A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Interacts with GPKOW.PTM Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.UniProtP68182Reactome Database ID Release 70163504Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=163504ReactomeR-RNO-1635041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-163504.1Reactome Database ID Release 70446977Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446977ReactomeR-RNO-4469771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446977.12Reactome Database ID Release 70446971Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446971ReactomeR-RNO-4469711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446971.11Reactome Database ID Release 70446967Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446967ReactomeR-RNO-4469671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446967.12PKA regulatory subunit:cAMP:Akap150,79:Iqgap1Reactome DB_ID: 44699211PKA regulatory subunit:cAMP ComplexReactome DB_ID: 44698524Reactome Database ID Release 70446985Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446985ReactomeR-RNO-4469851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446985.11Reactome Database ID Release 70446992Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446992ReactomeR-RNO-4469921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446992.1Reactome Database ID Release 70446974Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446974ReactomeR-RNO-4469741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446974.112938160Pubmed2003Identification of an IQGAP1/AKAP79 complex in beta-cellsNauert, JBRigas, JDLester, LBJ Cell Biochem 90:97-10811181538Pubmed2001Targeted protein kinase A and PP-2B regulate insulin secretion through reversible phosphorylationLester, LBFaux, MCNauert, JBScott, JDEndocrinology 142:1218-2719073898Pubmed2009Cell-permeable peptide-based disruption of endogenous PKA-AKAP complexes: a tool for studying the molecular roles of AKAP-mediated PKA subcellular anchoringFaruque, OMLe-Nguyen, DLajoix, ADVives, EPetit, PBataille, DHani, el-HAm J Physiol Cell Physiol 296:C306-169405718Pubmed1997Anchoring of protein kinase A facilitates hormone-mediated insulin secretionLester, LBLangeberg, LKScott, JDProc Natl Acad Sci U S A 94:14942-7