Reactome | PKA phosphorylates CREB1

PKA phosphorylates CREB1

Stable Identifier

R-HSA-111919

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

PRKACA,(PRKACB,PRKACG,PRKX) phosphorylates CREB1

ReviewStatus

5/5

Locations in the PathwayBrowser

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Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Parasitic Infection Pathways (Homo sapiens)
    - Leishmania infection (Homo sapiens)
      - Leishmania parasite growth and survival (Homo sapiens)
        
        Anti-inflammatory response favouring Leishmania parasite infection (Homo sapiens)
        
        ADORA2B mediated anti-inflammatory cytokines production (Homo sapiens)
        
        PKA phosphorylates CREB1 (Homo sapiens)
        
        FCGR3A-mediated IL10 synthesis (Homo sapiens)
        
        PKA phosphorylates CREB1 (Homo sapiens)

Neuronal System (Homo sapiens)

- Transmission across Chemical Synapses (Homo sapiens)
  - Neurotransmitter receptors and postsynaptic signal transmission (Homo sapiens)
    - Activation of NMDA receptors and postsynaptic events (Homo sapiens)
      - Post NMDA receptor activation events (Homo sapiens)
        
        CREB1 phosphorylation through the activation of Adenylate Cyclase (Homo sapiens)
        
        PKA phosphorylates CREB1 (Homo sapiens)

Signal Transduction (Homo sapiens)

- Intracellular signaling by second messengers (Homo sapiens)
  - DAG and IP3 signaling (Homo sapiens)
    - CaM pathway (Homo sapiens)
      - Calmodulin induced events (Homo sapiens)
        
        PKA-mediated phosphorylation of CREB (Homo sapiens)
        
        PKA phosphorylates CREB1 (Homo sapiens)
- Signaling by GPCR (Homo sapiens)
  - GPCR downstream signalling (Homo sapiens)
    - G alpha (i) signalling events (Homo sapiens)
      - Opioid Signalling (Homo sapiens)
        
        G-protein mediated events (Homo sapiens)
        
        PLC beta mediated events (Homo sapiens)
        
        Ca-dependent events (Homo sapiens)
        
        CaM pathway (Homo sapiens)
        
        Calmodulin induced events (Homo sapiens)
        
        PKA-mediated phosphorylation of CREB (Homo sapiens)
        
        PKA phosphorylates CREB1 (Homo sapiens)

General

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Protein kinase A (PKA) has two regulatory subunits and two catalytic subunits which are held together to form the holoenzyme and is activated upon binding of cAMP to the regulatory subunits. Once cAMP binds the regulatory subunits, the catalytic subunits are released to carry out phosphorylation of CREB1 at serine residue S133. Only the PKA catalytic subunit alpha, PRKACA, was directly demonstrated to phosphorylate CREB1 at S133, using recombinant mouse and rat proteins, respectively (Gonzalez and Montminy 1989). PKA catalytic subunits beta and gamma (PRKACB and PRKACG) are candidate CREB1 kinases based on indirect evidence and sequence similarity (Nagakura et al. 2002, Liang et al. 2007, James et al. 2009). PRKX is the catalytic subunit of the cAMP dependent protein kinase X, which shares the regulatory subunits and functional properties with the PKA. PRKX is highly expressed in the mouse fetal brain (Li et al. 2005) and is implicated in CREB1 phosphorylation through indirect evidence (Di Pasquale and Stacey 1998, Li et al. 2002).

Literature References

PubMed ID	Title	Journal	Year
15879576	Profiles of PrKX expression in developmental mouse embryo and human tissues Li, W, Yu, ZX, Kotin, RM	J. Histochem. Cytochem.	2005
2573431	Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133 Gonzalez, GA, Montminy, MR	Cell	1989
19244110	RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway James, MA, Lu, Y, Liu, Y, Vikis, HG, You, M	Cancer Res	2009
17908236	Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain Liang, Z, Liu, F, Grundke-Iqbal, I, Iqbal, K, Gong, CX	J Neurochem	2007
12150772	Impairment of cerebral cAMP-mediated signal transduction system and of spatial memory function after microsphere embolism in rats Nagakura, A, Takagi, N, Takeo, S	Neuroscience	2002
12082174	PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis Li, X, Li, HP, Amsler, K, Hyink, D, Wilson, PD, Burrow, CR	Proc. Natl. Acad. Sci. U.S.A.	2002
9733829	Adeno-associated virus Rep78 protein interacts with protein kinase A and its homolog PRKX and inhibits CREB-dependent transcriptional activation Di Pasquale, G, Stacey, SN	J. Virol.	1998

Participants

Input

Output

Participates

as an event of

Catalyst Activity

protein serine/threonine kinase activity of PRKACA,(PRKACB,PRKACG,PRKX) [nucleoplasm]

Physical Entity

PRKACA,(PRKACB,PRKACG,PRKX) [nucleoplasm] (Homo sapiens)

Activity

protein serine/threonine kinase activity (GO:0004674)

Inferred From

Prkaca phosphorylates Creb1 (Rattus norvegicus)

Authored

Le Novere, N (2004-03-31)

Jassal, B (2004-03-31)

Mahajan, SS (2009-10-29)

Reviewed

Castagnoli, L (2008-11-06)

Tukey, D (2009-11-18)

Yi, F (2018-11-02)

Hansen, KB (2018-11-02)

Created

Schmidt, EE (2004-03-25)