CK1/CDK5 Regulation Pathway

Preferred Label : CK1/CDK5 Regulation Pathway;

NCIt synonyms : CK1 CDK5 Regulation Pathway;

NCIt related terms : Regulation of ck1/cdk5 by type 1 glutamate receptors;

Alternative definition : BIOCARTA: Cdk5 is a cyclin dependent protein kinase involved in dopaminergic signaling in the neostriatal region of the brain. The role of cdk5 in dopamine responses occurs through phosphorylation of DARPP-32. Casein kinase 1 (CK1) also regulates DARPP-32 phosphorylation and dopamine signaling. The phosphorylation of DARPP-32 by cdk5 reduced dopamine signaling. Depending on its phosphorylation state, DARPP-32 inhibits either protein phosphatase 1 (PP1) or PKA. The role of mGLUR1 in this process is supported by the induction of cdk5 and CK1 activity by the mGLUR1 agonist DHPG and the subsequent phosphorylation of DARPP-32 associated with DHPG treatment of nigrostriatal neurons. CK-1 and Ckd5 inhibitors block the DHPG induced DARPP-32 phosphorylation. Dopamine exerts a positive signal that increases dopamine response by reversing phosphorylation of DARPP-32 at threonine-75. Dopamine initiates this pathway through activation of the D1 dopamine receptor, a Gs coupled GPCR, elevating cAMP and activating PKA. PKA activates protein phosphatase 2A (PP2A) which dephosphorylates DARPP-32 and increases dopamine responsiveness. This also removes the inhibition of PKA by DARPP-32, forming a positive feedback loop for further DARPP-32 inactivation by PKA. Activation of the D2 dopamine receptor has the opposite effect, shifting the DARPP-32 population toward the threonine-75 phosphorylated form. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_ck1Pathway;

Details

Origin ID

C39031;

UMLS CUI

C1511443;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Casein Kinase I Isoform Delta [NCIt concept]
- Cyclin-Dependent Kinase 5 [NCIt concept]
- Cyclin-Dependent Kinase 5 Activator 1 [NCIt concept]
- D(1A) Dopamine Receptor [NCIt concept]
- D(2) Dopamine Receptor [NCIt concept]
- Metabotropic Glutamate Receptor 1 [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Alpha Isoform [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Beta Isoform [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Gamma Isoform [NCIt concept]
- Serine/Threonine-Protein Phosphatase 2A Regulatory Subunit B'' Subunit Beta [NCIt concept]
- Serine/Threonine-Protein Phosphatase PP1-Alpha Catalytic Subunit [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Beta [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Gamma [NCIt concept]
- cAMP-Dependent Protein Kinase Type I-Alpha Regulatory Subunit [NCIt concept]
- cAMP-Dependent Protein Kinase Type II-Alpha Regulatory Subunit [NCIt concept]
pathway_has_gene_element
- CDK5 wt Allele [NCIt concept]
- CDK5R1 wt Allele [NCIt concept]
- CSNK1D wt Allele [NCIt concept]
- DRD1 wt Allele [NCIt concept]
- DRD2 wt Allele [NCIt concept]
- GRM1 wt Allele [NCIt concept]
- PPP1CA wt Allele [NCIt concept]
- PPP2R3B wt Allele [NCIt concept]
- PPP3CA wt Allele [NCIt concept]
- PPP3CB wt Allele [NCIt concept]
- PPP3CC wt Allele [NCIt concept]
- PRKACB wt Allele [NCIt concept]
- PRKACG wt Allele [NCIt concept]
- PRKAR1A wt Allele [NCIt concept]
- PRKAR2A wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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