Reactome | CaMK4 phosphorylates CREB1

CaMK4 phosphorylates CREB1

Stable Identifier

R-HSA-111912

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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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 CaMKII/CaMKK/CaMKIV cascasde (Homo sapiens)
        
        CaMK4 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)
        
        CaMK IV-mediated phosphorylation of CREB (Homo sapiens)
        
        CaMK4 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)
        
        CaMK IV-mediated phosphorylation of CREB (Homo sapiens)
        
        CaMK4 phosphorylates CREB1 (Homo sapiens)

General

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The cAMP-responsive element binding protein (CREB), a key regulator of gene expression, is activated by phosphorylation on Ser-133. Several different protein kinases possess the capability of driving this phosphorylation, making it a point of convergence for multiple intracellular signaling cascades. Work in neurons has indicated that physiologic synaptic stimulation recruits a fast calmodulin kinase IV (CaMKIV)-dependent pathway that dominates early signaling to CREB. Activated CaMKIV (CAMK4) phosphorylates CREB1 at S133, thereby initiating the transcription of CREB1-regulated set of genes, leading to protein synthesis and long lasting changes that underlie synaptic plasticity.

Literature References

PubMed ID	Title	Journal	Year
19001277	Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine Bilbao, A, Parkitna, JR, Engblom, D, Perreau-Lenz, S, Sanchis-Segura, C, Schneider, M, Konopka, W, Westphal, M, Breen, G, Desrivieres, S, Klugmann, M, Guindalini, C, Vallada, H, Laranjeira, R, de Fonseca, FR, Schumann, G, Schütz, G, Spanagel, R	Proc Natl Acad Sci U S A	2008

Participants

Input

Output

Participates

as an event of

Catalyst Activity

calcium/calmodulin-dependent protein kinase activity of p-S12.S13,T200-CAMK4:CALM1:4xCa2+ [nucleoplasm]

Physical Entity

p-S12.S13,T200-CAMK4:CALM1:4xCa2+ [nucleoplasm] (Homo sapiens)

Activity

calcium/calmodulin-dependent protein kinase activity (GO:0004683)

Inferred From

CaMKIV 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)

Lezza, AM (2013-12-07)

Tukey, D (2009-11-18)

Yi, F (2018-11-02)

Hansen, KB (2018-11-02)

Created

Schmidt, EE (2004-03-25)