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Information on EC 2.7.11.11 - cAMP-dependent protein kinase and Organism(s) Rattus norvegicus and UniProt Accession P27791
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2.7.11.11 cAMP-dependent protein kinaseIUBMB Comments
This eukaryotic enzyme recognizes the sequence -Arg-Arg-X-Ser*/Thr*-Hpo, where * indicates the phosphorylated residue and Hpo indicates a hydrophobic residue.The inactive holoenzyme is a heterotetramer composed of two regulatory (R) subunits and two catalytic (C) subunits. Each R subunit occludes the active site of a C subunit and contains two binding sites for 3',5'-cyclic-AMP (cAMP). Binding of cAMP activates the enzyme by causing conformational changes that release two free monomeric C subunits from a dimer of the R subunits, i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C. Activity requires phosphorylation of a conserved Thr in the activation loop (T-loop) sequence (Thr198 in human Calpha; Thr224 in budding yeast Tpk2), installed by auto-phosphorylation or by the 3-phosphoinositide-dependent protein kinase-1 (PDPK1). Certain R2C2 combinations can be localized to particular subcellular regions by their association with diverse species of 'A Kinase-Anchoring Proteins' (AKAPs). The enzyme has been characterized from many organisms. Humans have three C units (Calpha, Cbeta, and Cgamma) encoded by the paralogous genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits (R1alpha, RIbeta, RIIalpha and RIIbeta), encoded by PKRAR1A, PKRAR1B, PKRAR2A and PKRAR2B, respectively. Yeast (Saccharomyces cerevisiae) has three C subunits (Tpk1, Tpk2, and Tpk3) encoded by the paralogous genes TPK1, TPK2 and TPK3, respectively, and a single R subunit (Bcy1) encoded by the BCY1 gene. Some validated substrates of the enzyme include cAMP-response element-binding protein (CREB), phosphorylase kinase alpha subunit (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, Nej1, and Pyk1 in yeast.
Specify your search results
Word Map
- 2.7.11.11
- cyclase
- forskolin
- agonist
- adenylate
- phosphodiesterase
- cardiac
-
adenylyl
- phosphoprotein
- isoproterenol
- synaptic
-
holoenzyme
- cgmp
-
phorbol
-
dibutyryl
- a-kinase
- prostaglandin
- calmodulin
-
cgmp-dependent
-
beta-adrenergic
- creb
- phosphopeptide
-
desensitization
-
akaps
- autophosphorylation
-
camp-mediated
-
gamma-32patp
- pki
- rp-camps
-
pka-dependent
-
camp-responsive
-
sarcoplasmic
-
l-type
- phospholamban
-
8-br-camp
- 8-bromo-camp
-
calmodulin-dependent
-
pka-mediated
-
camp-independent
-
patch-clamp
- 3',5'-monophosphate
- ibmx
-
camp-induced
- 3-isobutyl-1-methylxanthine
- isoprenaline
-
camp-regulated
-
camp-stimulated
- dibutyryl-camp
-
phosphorylatable
- rolipram
-
phospholipid-dependent
- medicine
- drug development
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
camp-dependent protein kinase, a kinase, cyclic amp-dependent protein kinase, camp-pka, camp/protein kinase a, capk, prkaca, camp dependent protein kinase, camp-dependent pka, cyclic amp-dependent protein kinase a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A kinase
-
-
-
-
ATP:protein phosphotransferase (cAMP-dependent)
-
-
-
-
cAMP-dependent protein kinase
-
-
-
-
PK-25
-
-
-
-
PKA
PKA C-alpha
-
-
-
-
PKA C-beta
-
-
-
-
PKA C-gamma
-
-
-
-
PKA catalytic (C) subunit
-
-
-
-
protein kinase A
PKA
-
-
-
-
PKA
-
-
protein kinase A
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
the substrate binds to the regulatory subunit which is released from the catalytic subunit for enzyme activity, mechanism and structure-function relationship
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein Ser/Thr-phosphotransferase (3',5'-cAMP-dependent)
This eukaryotic enzyme recognizes the sequence -Arg-Arg-X-Ser*/Thr*-Hpo, where * indicates the phosphorylated residue and Hpo indicates a hydrophobic residue.The inactive holoenzyme is a heterotetramer composed of two regulatory (R) subunits and two catalytic (C) subunits. Each R subunit occludes the active site of a C subunit and contains two binding sites for 3',5'-cyclic-AMP (cAMP). Binding of cAMP activates the enzyme by causing conformational changes that release two free monomeric C subunits from a dimer of the R subunits, i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C. Activity requires phosphorylation of a conserved Thr in the activation loop (T-loop) sequence (Thr198 in human Calpha; Thr224 in budding yeast Tpk2), installed by auto-phosphorylation or by the 3-phosphoinositide-dependent protein kinase-1 (PDPK1). Certain R2C2 combinations can be localized to particular subcellular regions by their association with diverse species of 'A Kinase-Anchoring Proteins' (AKAPs). The enzyme has been characterized from many organisms. Humans have three C units (Calpha, Cbeta, and Cgamma) encoded by the paralogous genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits (R1alpha, RIbeta, RIIalpha and RIIbeta), encoded by PKRAR1A, PKRAR1B, PKRAR2A and PKRAR2B, respectively. Yeast (Saccharomyces cerevisiae) has three C subunits (Tpk1, Tpk2, and Tpk3) encoded by the paralogous genes TPK1, TPK2 and TPK3, respectively, and a single R subunit (Bcy1) encoded by the BCY1 gene. Some validated substrates of the enzyme include cAMP-response element-binding protein (CREB), phosphorylase kinase alpha subunit (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, Nej1, and Pyk1 in yeast.
CAS REGISTRY NUMBER
COMMENTARY
142008-29-5
-
142008-29-5
cAMP-dependent protein kinase
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + cAMP response element binding protein
ADP + cAMP response element binding protein
-
-
-
-
?
ATP + cAMP response element binding protein
ADP + phosphorylated cAMP response element binding protein
-
the transcription factor cAMP response element binding protein is directly activated by PKA
-
-
?
ATP + cAMP-response element-binding protein
ADP + phosphorylated cAMP-response element-binding protein
ATP + lactate dehydrogenase subunit A mRNA
ADP + 3'-UTR phosphorylated lactate dehydrogenase subunit A mRNA
ATP + low-density lipoprotein-related protein
ADP + phosphorylated low-density lipoprotein-related protein
-
-
-
-
?
ATP + NDUFS4 subunit of complex I
ADP + phosphorylated NDUFS4 subunit of complex I
-
complex I is the NADH-ubiquinone oxidoreductase, E.C 1.6.5.3
-
-
?
ATP + phosphodiesterase-4
ADP + phosphorylated phosphodiesterase-4
-
-
-
-
?
ATP + protein tyrosine phosphatase
ADP + phosphorylated protein tyrosine phosphatase
-
i.e. PTP, contains a PEST motif
-
-
?
ATP + ribosomal S6 protein
ADP + phosphorylated ribosomal S6 protein
-
-
-
-
?
ATP + stathmin
ADP + phosphorylated stathmin
-
phosphorylation at Ser63
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
-
4 isoforms of the human enzyme as substrate, phosphorylation at Ser40 of the regulatory subunit of the substrate results in release of bound inhibiting catecholamines, e.g. dopamine and dihydroxyphenylalanine, from the tyrosine hydroxylase
-
-
?
ATP + VASP
ADP + phosphorylated VASP
-
i.e. vasodilator-stimulated phosphoprotein
-
-
?
ATP + [cystic fibrosis transmembrane conductance regulator protein]
ADP + [cystic fibrosis transmembrane conductance regulator phosphoprotein]
-
-
-
-
?
ATP + A-kinase anchor protein
ADP + phosphorylated A-kinase anchor protein
-
phosphorylation at Ser1928
-
-
?
ATP + A-kinase anchor protein
ADP + phosphorylated A-kinase anchor protein
-
i.e. AKAP, phosphorylation at Ser1928, the rat enzyme is active with different AKAP substrate variants from different sources, overview
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-cateniin
-
phosphorylation on Ser552 and Ser675
-
-
?
ATP + cAMP-response element-binding protein
ADP + phosphorylated cAMP-response element-binding protein
-
-
-
-
?
ATP + cAMP-response element-binding protein
ADP + phosphorylated cAMP-response element-binding protein
-
phosphorylation at Ser133
-
-
?
ATP + Cav1.2
ADP + phosphorylated Cav1.2
-
in anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons plays a critical role involving phosphorylation by the enzyme, PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation in heart and brain
-
-
?
ATP + Cav1.2
ADP + phosphorylated Cav1.2
-
an L-type calcium channel Cav1.2
-
-
?
ATP + IP3R-2
ADP + phosphorylated IP3R-2
-
phosphoregulation of the inositol 1,4,5-trisphosphate receptor subtype 2, PKA enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2J cells, regulation, overview
-
-
?
ATP + lactate dehydrogenase subunit A mRNA
ADP + 3'-UTR phosphorylated lactate dehydrogenase subunit A mRNA
-
-
-
-
?
ATP + lactate dehydrogenase subunit A mRNA
ADP + 3'-UTR phosphorylated lactate dehydrogenase subunit A mRNA
-
the enzyme stabilizes lactate dehydrogenase LDH-A mRNA and increases intracellular LDH-A mRNA levels by phosphorylation of a cAMP-stabilizing region CSR on the 3'-untranslated region of the LDH-A mRNA, regulation, mechanism
-
-
?
ATP + RGS protein
ADP + RGS protein phosphate
-
recombinant HA-tagged substrate expressed in B35 cells, phosphorylation of RGS14 by PKA potentiates its activity toward Galphai-GDP
-
-
?
ATP + RGS protein
ADP + RGS protein phosphate
-
i.e. regulator of G protein signaling protein, recombinant His-tagged substrate R14-RSG residues 1-205 and 299-544, phosphorylation of wild-type R14-RSG at Ser258 and Thr494
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
abnormal hyperphosphorylation of tau by PKA is associated with Alzheimer's disease and other tauopathies leading to neuronal degeneration
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation by PKA at Ser214, PKA catalyzes the reaction of EC 2.7.11.26 in brain
-
-
?
additional information
?
-
-
cAMP-dependent activation of BKCa channels in pulmonary arterial smooth muscle is not catalyzed by PKA but by cGMP-dependent protein kinase PKG, thus PKA is not involved in cAMP-induced signaling in pulmonary vasodilation
-
-
?
additional information
?
-
-
induced by the pituitary follicle-stimulating hormone FSH PKA also catalyzes the dephosphorylation of residues T421 and S424 of the autoinhibitory domain of p70S6K, resulting in activation of p70S6K important for differentiation of Sertoli cells in male reproduction, regulation overview
-
-
?
additional information
?
-
-
PKA regulatory and catalytic subunits are bound in the CSR complex including the protein kinase A anchoring protein AKAP 95 and several CSR-binding proteins, the complex acts in stabilizing the LDH-A mRNA, overview
-
-
?
additional information
?
-
-
tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain, inhibition of tau hyperphosphorylation inhibits an associated loss in spatial memory
-
-
?
additional information
?
-
-
the enzyme is not required for adenosine-induced dilation of intracerebral arterioles and regulation of cerebral blood flow
-
-
?
additional information
?
-
-
the enzyme plays a paradoxical role in cell motility facilitating and inhibiting actin cytoskeletal dynamics and cell migration, overview, the enzyme is regulated in a subcellular space during cell migration, regulatory subunits RII are enriched in protrusive cellular structures and pseudopodia formed during chemotaxis, anchoring of PKA inhibits pseudopod formation and cell migration, regulation of the process overview
-
-
?
additional information
?
-
-
cAMP elevation in the Schwann cell is sufficient to induce E-cadherin expression accompanied by suppression of N-cadherin expression
-
-
?
additional information
?
-
-
cAMP-dependent neurite outgrowth is mediated by PKA
-
-
?
additional information
?
-
-
exchange protein activated by cAMP acts synergistically with PKA in cAMP-mediated mitogenesis
-
-
?
additional information
?
-
-
autophosphorylation of the PKA type II regulatory subunit (RII) can alter its affinity for protein kinase A-anchoring proteins and the catalytic subunit of PKA, RII phosphorylation regulates PKA-dependent substrate phosphorylation and may have significant implications for modulation of cardiac function
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + A-kinase anchor protein
ADP + phosphorylated A-kinase anchor protein
-
phosphorylation at Ser1928
-
-
?
ATP + cAMP-response element-binding protein
ADP + phosphorylated cAMP-response element-binding protein
-
phosphorylation at Ser133
-
-
?
ATP + Cav1.2
ADP + phosphorylated Cav1.2
-
in anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons plays a critical role involving phosphorylation by the enzyme, PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation in heart and brain
-
-
?
ATP + IP3R-2
ADP + phosphorylated IP3R-2
-
phosphoregulation of the inositol 1,4,5-trisphosphate receptor subtype 2, PKA enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2J cells, regulation, overview
-
-
?
ATP + lactate dehydrogenase subunit A mRNA
ADP + 3'-UTR phosphorylated lactate dehydrogenase subunit A mRNA
-
the enzyme stabilizes lactate dehydrogenase LDH-A mRNA and increases intracellular LDH-A mRNA levels by phosphorylation of a cAMP-stabilizing region CSR on the 3'-untranslated region of the LDH-A mRNA, regulation, mechanism
-
-
?
ATP + NDUFS4 subunit of complex I
ADP + phosphorylated NDUFS4 subunit of complex I
-
complex I is the NADH-ubiquinone oxidoreductase, E.C 1.6.5.3
-
-
?
ATP + RGS protein
ADP + RGS protein phosphate
-
recombinant HA-tagged substrate expressed in B35 cells, phosphorylation of RGS14 by PKA potentiates its activity toward Galphai-GDP
-
-
?
ATP + ribosomal S6 protein
ADP + phosphorylated ribosomal S6 protein
-
-
-
-
?
ATP + stathmin
ADP + phosphorylated stathmin
-
phosphorylation at Ser63
-
-
?
ATP + [cystic fibrosis transmembrane conductance regulator protein]
ADP + [cystic fibrosis transmembrane conductance regulator phosphoprotein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
abnormal hyperphosphorylation of tau by PKA is associated with Alzheimer's disease and other tauopathies leading to neuronal degeneration
-
-
?
additional information
?
-
-
cAMP-dependent activation of BKCa channels in pulmonary arterial smooth muscle is not catalyzed by PKA but by cGMP-dependent protein kinase PKG, thus PKA is not involved in cAMP-induced signaling in pulmonary vasodilation
-
-
?
additional information
?
-
-
induced by the pituitary follicle-stimulating hormone FSH PKA also catalyzes the dephosphorylation of residues T421 and S424 of the autoinhibitory domain of p70S6K, resulting in activation of p70S6K important for differentiation of Sertoli cells in male reproduction, regulation overview
-
-
?
additional information
?
-
-
PKA regulatory and catalytic subunits are bound in the CSR complex including the protein kinase A anchoring protein AKAP 95 and several CSR-binding proteins, the complex acts in stabilizing the LDH-A mRNA, overview
-
-
?
additional information
?
-
-
tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain, inhibition of tau hyperphosphorylation inhibits an associated loss in spatial memory
-
-
?
additional information
?
-
-
the enzyme is not required for adenosine-induced dilation of intracerebral arterioles and regulation of cerebral blood flow
-
-
?
additional information
?
-
-
the enzyme plays a paradoxical role in cell motility facilitating and inhibiting actin cytoskeletal dynamics and cell migration, overview, the enzyme is regulated in a subcellular space during cell migration, regulatory subunits RII are enriched in protrusive cellular structures and pseudopodia formed during chemotaxis, anchoring of PKA inhibits pseudopod formation and cell migration, regulation of the process overview
-
-
?
additional information
?
-
-
cAMP elevation in the Schwann cell is sufficient to induce E-cadherin expression accompanied by suppression of N-cadherin expression
-
-
?
additional information
?
-
-
cAMP-dependent neurite outgrowth is mediated by PKA
-
-
?
additional information
?
-
-
exchange protein activated by cAMP acts synergistically with PKA in cAMP-mediated mitogenesis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(Rp)-adenosine 3',5'-cyclic monophosphorothionate triethyl ammonium salt
-
inhibitor of PKA
Acetylsalicylic acid
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
H2O2
-
H2O2 inhibits activation of PKA, but inhibition can be reverted with dithiothreitol or with thioredoxin reductase plus thioredoxin, H2O2 is ineffective if the PKA holoenzyme is preincubated with cAMP, if added to the catalytic alpha-subunit, which is active independently of cAMP activation, or if the catalytic alpha-subunit is substituted by ist C199A mutant in the reconstituted holoenzyme
KN-93
-
cAMP-dependent PKA activity of prazosin-stimulated hepatocytes is suppressed
N-[2-(4-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride
-
-
naproxen
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
nimesulide
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
piroxicam
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
Rp-cAMP
-
0.5 mM significantly reduces forskolin- and dibutyryl-cAMP-induced PKA activation
Trifluoperazine
-
cAMP-dependent PKA activity of prazosin-stimulated hepatocytes is suppressed
U-73122
-
cAMP-dependent PKA activity of prazosin-stimulated hepatocytes is suppressed
H-89
-
0.02 mM significantly reduces forskolin- and dibutyryl-cAMP-induced PKA activation
additional information
-
complete enzyme inhibition inhibits pseudopod formation and cell migration
-
additional information
-
cyclo-oxygenase-independent inhibitory effect of non-steroidal anti-inflammatory drugs, mechanism, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
D-glucose
-
increases phosphorylation of beta-catenin on Ser552 in INS-1E beta-cells
N6,2'-O-dibutyryl-cAMP
-
increases phosphorylation of beta-catenin on Ser552 in INS-1E beta-cells
N6-monobutyryl-3'-5'-cAMP
-
specific protein kinase A activator, direct stimulation of acivity with 1 mM N6-monobutyryl-3'-5'-cAMP is necessary for the alkaline pH-induced accumulation of vacuolar H+-ATPase in clear cell apical microvilli
Sp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate
-
activates PKA
cAMP
-
each monomer of the tetrameric enzyme contains 2 bindig sites A and B for cAMP, binding involves Arg230 of domain A and Arg359 in domain B of regulatory subunit RIIbeta, cAMP binding releases the catalytic subunits
forskolin
-
alone increases activity, which is further increased by the addition of forskolin plus dibutyryl-cAMP and phosphodiesterase inhibitor IBMX
additional information
-
dephosphorylation activity induced by the pituitary follicle-stimulating hormone FSH
-
additional information
-
forskolin activates via stimulation of cAMP production
-
additional information
-
forskolin stimulates the adenylyl cyclase, which activates the enzyme by increased cAMP level
-
additional information
-
beta-adrenergic stimulation of Ser1928 phosphorylation, L-type calcium channel Cav1.2 constitutively associates with the beta2-AR and PKA to efficiently respond to beta-adrenergic activation
-
additional information
-
not stimulated by glial growth factor, sensory and motor neuron derived factor, or platelet-derived growth factor
-
additional information
-
no intracellular activating effect by sodium lactate
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics for cAMP binding to wild-type and mutant regulatory subunits RIIbeta, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0039
7-hydroxystaurosporine
-
recombinant wild-type catalytic subunit, pH 7.5
0.0049
7-hydroxystaurosporine
-
recombinant mutant S338A catalytic subunit, pH 7.5
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
localization of cAMP-dependent protein kinase, composed of the components C-PKA, R-PKA, and AKAP121, associated with the A-kinase anchor protein in the inner mitochondrial compartment
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the contraction and relaxation of the heart is controlled by stimulation of the b1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation
physiological function
malfunction
metabolism
physiological function
physiological function
protein phosphorylation by cAMP-dependent protein kinase (PKA) triggers cellular changes, including fight-or-flight responses in heart cells, and synaptic potentiation in neurons
physiological function
uncontrolled activity of PKA catalytic subunits is pathological
malfunction
-
inhibition of PKA reduces accuracy in the 5-choice serial reaction time task and causes substantial increases in locomotor activity without affecting motivation or the capacity to emit operant responses at high rates, PKA inhibition within the medial prefrontal cortex of rats produces inattention and hyperactivity
malfunction
-
inhibition of PKA with KT5720 abolishes lactic-acid- or contraction-induced ATP release from muscle
metabolism
-
the cAMP/PKA pathway is involved in the signal transduction pathway for cystic fibrosis transmembrane conductance regulator-regulated ATP release from muscle
metabolism
-
prazosin-stimulated release of hepatic triacylglyceride lipase (HTGL) from hepatocytes is caused by activation of protein kinase A (PKA) associated with stimulation of Ca2+/calmodulin-dependent protein kinase II (CaMK-II) activity through a signal cascade from phospholipase C
physiological function
-
PKA activates phosphodiesterase-4 and increases the sensitivity of phosphodiesterase-4 to inhibition by rolipram
physiological function
-
cAMP and PKA are involved in the activation of cystic fibrosis transmembrane conductance regulator, CFTR, during muscle contractions or acidosis. CFTR is involved in the release of ATP from the contracting skeletal muscle in vivo, role of intracellular cAMP in stimulating the increase in extracellular ATP at low pH
physiological function
-
PKA catalyzed phosphorylation of beta-catenin at Ser552 and Ser675 results in stabilization of the protein and activation of its transcriptional activity. beta-Catenin is required for the glucose-dependent increase in cyclin D1 expression in INS-1E beta-cells
physiological function
-
the cAMP-dependent protein kinase regulates post-translational processing and expression of complex I subunits in mammalian cells, it promotes the activity of complex I and lowers reactive oxygen species level in mammalian cell cultures, overview. cAMP-dependent phosphorylation of the NDUFS4 subunit of the complex promotes the import in mitochondria of this nuclear encoded protein
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KAPCA_RAT
351
0
40620
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
121000
-
x * 57000, C-subunit, SDS-PAGE, x * 48000, RII-subunit, SDS-PAGE, x * 121000, AKAP121, SDS-PAGE
48000
-
x * 57000, C-subunit, SDS-PAGE, x * 48000, RII-subunit, SDS-PAGE, x * 121000, AKAP121, SDS-PAGE
57000
-
x * 57000, C-subunit, SDS-PAGE, x * 48000, RII-subunit, SDS-PAGE, x * 121000, AKAP121, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterotetramer
PKA is a heterotetrameric kinase comprising two regulatory and two catalytic subunits. Binding of two molecules of cAMP to each of the two regulatory subunits (PKA-R) induces the release of the active catalytic subunits (PKA-C)
?
-
x * 57000, C-subunit, SDS-PAGE, x * 48000, RII-subunit, SDS-PAGE, x * 121000, AKAP121, SDS-PAGE
tetramer
additional information
tetramer
-
2 regulatory subunits in a dimer bound to 2 catalytic subunits, the latter are released during activation by cAMP
tetramer
-
consists of two regulatory and two catalytic subunits, the regulatory subunits of PKA bind to free catalytic subunits (alpha, beta, gamma, or PRkX) and their primary function appears to keep the catalytic subunits in an inactive state, two molecules of cAMP bind to each regulatory subunit of PKA and causes the subsequent release and activation of the catalytic subunits
additional information
catalytic subunits are released from regulatory subunits by cAMP. Regulatory subunits are expressed much more highly than catalytic subunits to support rapid catalytic subunit reassociation
additional information
-
catalytic subunit residue Ser338 stabilizes the enzyme
additional information
-
the substrate binds to the regulatory subunit which is released from the catalytic subunit for enzyme activity
additional information
-
PKA is composed of the components C-PKA, R-PKA, and AKAP121
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C199A
-
the mutant of the catalytic alpha-subunit in the holoenzyme leads to insensitivity towards H2O2
R230K
-
site-directed mutagenesis, mutation of an A domain residue of regulatory subunit RIIbeta, the mutant possesses one high-affinity cAMP binding site and one low active binding site resulting in reduced overall cAMP binding
R359K
-
site-directed mutagenesis, mutation of a B domain residue of regulatory subunit RIIbeta, the mutant possesses one high-affinity cAMP binding site and one low active binding site resulting in reduced overall cAMP binding
S338A
-
site-specific mutagenesis, mutation of a residue in the hydrophobic motif at the C-terminus of the catalytic subunit, catalytic activity is similar to the wild-type catalytic subunit, reduced protein stability compared to the wild-type enzyme
T197A
-
site-specific mutagenesis, mutation of activation loop residue of the catalytic subunit, inactive mutant, conformational changes and reduced protein stability compared to the wild-type enzyme
T197A/S338A
-
site-specific mutagenesis, highly unstable protein, tends to aggregation
additional information
additional information
-
construction of a deletion mutant of regulatory subunit RIIbeta lacking the complete domain B
additional information
-
deletion of the AKAP150 gene abrogates stimulation of alpha11.2 phosphorylation on Ser1928 in vivo, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged catalytic subunit C, and His-tagged wild-type and mutant regulatory subunits RIIbeta, by nickel affinity chromatography and dialysis
-
regulatory subunit RII from C6 cells by affinity chromatography on an 8-(6-aminohexyl)-amino-cAMP-resin
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
isolation of a full length cDNA clone encoding the C alpha type catalytic subunit of cAMP-dependent protein kinase
expression of His-tagged catalytic subunit C, and His-tagged wild-type and mutant regulatory subunits RIIbeta
-
subcloning and expression of His-tagged wild-type and mutant PKA catalytic subunits in Escherichia coli strain BL21(DE3), introduction of a tobacco etch virus cleavage site to remove the tag, expression of deuterated catalytic subunit in Escherichia coli strain CT19
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reversible unfolding and folding in 8.5 M urea of recombinant His-tagged wild-type and mutant regulatory subunits RIIbeta, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
PKA is a target for the therapeutic treatment of Alzheimer's disease and other tauopathies
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wiemann, S.; Voss, H.; Kinzel, V.; Pyerin, W.
Rat C alpha catalytic subunit of the cAMP-dependent protein kinase: cDNA sequence and evidence that it is the only isoform expressed in myoblasts
Biochim. Biophys. Acta
1089
254-256
1991
Rattus norvegicus (P27791)
Barman, S.A.; Zhu, S.; Han, G.; White, R.E.
cAMP activates BKCa channels in pulmonary arterial smooth muscle via cGMP-dependent protein kinase
Am. J. Physiol.
284
L1004-1011
2003
Rattus norvegicus
Hollinger, S.; Ramineni, S.; Hepler, J.R.
Phosphorylation of RGS14 by protein kinase A potentiates its activity toward Galphai
Biochemistry
42
811-819
2003
Rattus norvegicus
Langer, T.; Vogtherr, M.; Elshorst, B.; Betz, M.; Schieborr, U.; Saxena, K.; Schwalbe, H.
NMR backbone assignment of a protein kinase catalytic domain by a combination of several approaches: application to the catalytic subunit of cAMP-dependent protein kinase
ChemBioChem
5
1508-1516
2004
Rattus norvegicus
Liu, S.J.; Zhang, J.Y.; Li, H.L.; Fang, Z.Y.; Wang, Q.; Deng, H.M.; Gong, C.X.; Grundke-Iqbal, I.; Iqbal, K.; Wang, J.Z.
Tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain
J. Biol. Chem.
279
50078-50088
2004
Rattus norvegicus
Zawadzki, K.M.; Taylor, S.S.
cAMP-dependent protein kinase regulatory subunit type IIbeta: active site mutations define an isoform-specific network for allosteric signaling by cAMP
J. Biol. Chem.
279
7029-7036
2004
Rattus norvegicus
Jungmann, R.A.; Kiryukhina, O.
Cyclic AMP and AKAP-mediated targeting of protein kinase A regulates lactate dehydrogenase subunit A mRNA stability
J. Biol. Chem.
280
25170-25177
2005
Rattus norvegicus
West, G.A.; Meno, J.R.; Nguyen, T.S.; Ngai, A.C.; Simard, J.M.; Winn, H.R.
cGMP-dependent and not cAMP-dependent kinase is required for adenosine-induced dilation of intracerebral arterioles
J. Cardiovasc. Pharmacol.
41
444-451
2003
Rattus norvegicus
Sura, G.R.; Daubner, S.C.; Fitzpatrick, P.F.
Effects of phosphorylation by protein kinase A on binding of catecholamines to the human tyrosine hydroxylase isoforms
J. Neurochem.
90
970-978
2004
Rattus norvegicus
Lecureuil, C.; Tesseraud, S.; Kara, E.; Martinat, N.; Sow, A.; Fontaine, I.; Gauthier, C.; Reiter, E.; Guillou, F.; Crepieux, P.
Follicle-stimulating hormone activates p70 ribosomal protein S6 kinase by protein kinase A-mediated dephosphorylation of Thr 421/Ser 424 in primary Sertoli cells
Mol. Endocrinol.
19
1812-1820
2005
Rattus norvegicus
Howe, A.K.; Baldor, L.C.; Hogan, B.P.
Spatial regulation of the cAMP-dependent protein kinase during chemotactic cell migration
Proc. Natl. Acad. Sci. USA
102
14320-14325
2005
Homo sapiens, Rattus norvegicus
Zentella de Pina, M.; Vazquez-Meza, H.; Agundis, C.; Pereyra, M.A.; Pardo, J.P.; Villalobos-Molina, R.; Pina, E.
Inhibition of cAMP-dependent protein kinase A: a novel cyclo-oxygenase-independent effect of non-steroidal anti-inflammatory drugs in adipocytes
Auton. Autacoid. Pharmacol.
27
85-92
2007
Bos taurus, Rattus norvegicus
Hall, D.D.; Davare, M.A.; Shi, M.; Allen, M.L.; Weisenhaus, M.; McKnight, G.S.; Hell, J.W.
Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons
Biochemistry
46
1635-1646
2007
Rattus norvegicus
Sardanelli, A.M.; Signorile, A.; Nuzzi, R.; Rasmo, D.D.; Technikova-Dobrova, Z.; Drahota, Z.; Occhiello, A.; Pica, A.; Papa, S.
Occurrence of A-kinase anchor protein and associated cAMP-dependent protein kinase in the inner compartment of mammalian mitochondria
FEBS Lett.
580
5690-5696
2006
Rattus norvegicus
Regimbald-Dumas, Y.; Arguin, G.; Fregeau, M.O.; Guillemette, G.
cAMP-dependent protein kinase enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2J cells
J. Cell. Biochem.
101
609-618
2007
Rattus norvegicus
Pastor-Soler, N.M.; Hallows, K.R.; Smolak, C.; Gong, F.; Brown, D.; Breton, S.
Alkaline pH- and cAMP-induced V-ATPase membrane accumulation is mediated by protein kinase A in epididymal clear cells
Am. J. Physiol. Cell Physiol.
294
C488-C494
2008
Rattus norvegicus
Wojtal, K.A.; Hoekstra, D.; van Ijzendoorn, S.C.
cAMP-dependent protein kinase A and the dynamics of epithelial cell surface domains: moving membranes to keep in shape
Bioessays
30
146-155
2008
Rattus norvegicus
Crawford, A.T.; Desai, D.; Gokina, P.; Basak, S.; Kim, H.A.
E-cadherin expression in postnatal Schwann cells is regulated by the cAMP-dependent protein kinase A pathway
Glia
56
1637-1647
2008
Rattus norvegicus
de Pina, M.Z.; Vazquez-Meza, H.; Pardo, J.P.; Rendon, J.L.; Villalobos-Molina, R.; Riveros-Rosas, H.; Pina, E.
Signaling the signal, cyclic AMP-dependent protein kinase inhibition by insulin-formed H2O2 and reactivation by thioredoxin
J. Biol. Chem.
283
12373-12386
2008
Bos taurus, Rattus norvegicus
Manni, S.; Mauban, J.H.; Ward, C.W.; Bond, M.
Phosphorylation of the cAMP-dependent protein kinase (PKA) regulatory subunit modulates PKA-AKAP interaction, substrate phosphorylation, and calcium signaling in cardiac cells
J. Biol. Chem.
283
24145-24154
2008
Rattus norvegicus
Hochbaum, D.; Hong, K.; Barila, G.; Ribeiro-Neto, F.; Altschuler, D.L.
Epac, in synergy with cAMP-dependent protein kinase (PKA), is required for cAMP-mediated mitogenesis
J. Biol. Chem.
283
4464-4468
2008
Rattus norvegicus
Mustafa, S.B.; Castro, R.; Falck, A.J.; Petershack, J.A.; Henson, B.M.; Mendoza, Y.M.; Choudary, A.; Seidner, S.R.
Protein kinase A and mitogen-activated protein kinase pathways mediate cAMP induction of alpha-epithelial Na+ channels (alpha-ENaC)
J. Cell. Physiol.
215
101-110
2008
Rattus norvegicus
Tomimatsu, N.; Arakawa, Y.
Survival-promoting activity of pituitary adenylate cyclase-activating polypeptide in the presence of phosphodiesterase inhibitors on rat motoneurons in culture: cAMP-protein kinase A-mediated survival
J. Neurochem.
107
628-635
2008
Rattus norvegicus
Aglah, C.; Gordon, T.; Posse de Chaves, E.I.
cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons
Neuropharmacology
55
8-17
2008
Rattus norvegicus
Dai, R.; Ali, M.K.; Lezcano, N.; Bergson, C.
A crucial role for cAMP and protein kinase A in D1 dopamine receptor regulated intracellular calcium transients
Neurosignals
16
112-123
2008
Homo sapiens, Rattus norvegicus
Paine, T.A.; Neve, R.L.; Carlezon, W.A.
Attention deficits and hyperactivity following inhibition of cAMP-dependent protein kinase (PKA) within the medial prefrontal cortex of rats
Neuropsychopharmacology
34
2143-2155
2009
Rattus norvegicus
Itoh, T.; Abe, K.; Hong, J.; Inoue, O.; Pike, V.W.; Innis, R.B.; Fujita, M.
Effects of cAMP-dependent protein kinase activator and inhibitor on in vivo rolipram binding to phosphodiesterase 4 in conscious rats
Synapse
64
172-176
2010
Rattus norvegicus
Cognard, E.; Dargaville, C.G.; Hay, D.L.; Shepherd, P.R.
Identification of a pathway by which glucose regulates beta-catenin signalling via the cAMP/protein kinase A pathway in beta-cell models
Biochem. J.
449
803-811
2013
Rattus norvegicus
Papa, S.; Scacco, S.; De Rasmo, D.; Signorile, A.; Papa, F.; Panelli, D.; Nicastro, A.; Scaringi, R.; Santeramo, A.; Roca, E.; Trentadue, R.; Larizza, M.
cAMP-dependent protein kinase regulates post-translational processing and expression of complex I subunits in mammalian cells
Biochim. Biophys. Acta
1797
649-658
2010
Homo sapiens, Mus musculus, Rattus norvegicus, Mus musculus BALB/c
Tu, J.; Lu, L.; Cai, W.; Ballard, H.J.
cAMP/protein kinase A activates cystic fibrosis transmembrane conductance regulator for ATP release from rat skeletal muscle during low pH or contractions
PLoS ONE
7
e50157
2012
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Yip, Y.Y.; Yeap, Y.Y.; Bogoyevitch, M.A.; Ng, D.C.
cAMP-dependent protein kinase and c-Jun N-terminal kinase mediate Stathmin phosphorylation for the maintenance of interphase microtubules during osmotic stress
J. Biol. Chem.
289
2157-2169
2014
Rattus norvegicus
Diering, S.; Stathopoulou, K.; Goetz, M.; Rathjens, L.; Harder, S.; Piasecki, A.; Raabe, J.; Schulz, S.; Brandt, M.; Pflaumenbaum, J.; Fuchs, U.; Donzelli, S.; Sadayappan, S.; Nikolaev, V.O.; Flenner, F.; Ehler, E.; Cuello, F.
Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents
J. Biol. Chem.
295
15342-15365
2020
Rattus norvegicus (P27791)
Nakamura, T.; Kamishikiryo, J.; Morita, T.
Prazosin-stimulated release of hepatic triacylglyceride lipase from primary cultured rat hepatocytes is involved in the regulation of cAMP-dependent protein kinase through activation of the Ca(2+)/calmodulin-dependent protein kinase-II
Pharmacol. Rep.
68
649-653
2016
Rattus norvegicus
Walker-Gray, R.; Stengel, F.; Gold, M.G.
Mechanisms for restraining cAMP-dependent protein kinase revealed by subunit quantitation and cross-linking approaches
Proc. Natl. Acad. Sci. USA
114
10414-10419
2017
Homo sapiens (P22694), Homo sapiens, Rattus norvegicus (P27791), Rattus norvegicus Sprague-Dawley (P27791)
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