RGD Reference Report - DARPP-32, Jack of All Trades... Master of Which? - Rat Genome Database

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DARPP-32, Jack of All Trades... Master of Which?

Authors: Yger, M  Girault, JA 
Citation: Yger M and Girault JA, Front Behav Neurosci. 2011 Sep 8;5:56. doi: 10.3389/fnbeh.2011.00056. eCollection 2011.
RGD ID: 11041163
Pubmed: PMID:21927600   (View Abstract at PubMed)
PMCID: PMC3168893   (View Article at PubMed Central)
DOI: DOI:10.3389/fnbeh.2011.00056   (Journal Full-text)

DARPP-32 (PPP1R1B) was discovered as a substrate of cAMP-dependent protein kinase (PKA) enriched in dopamine-innervated brain areas. It is one of three related, PKA-regulated inhibitors of protein phosphatase-1 (PP1). These inhibitors seem to have appeared in early vertebrate ancestors, possibly Gnathostomes. DARPP-32 has additional important biochemical properties including inhibition of PKA when phosphorylated by Cdk5 and regulation by casein kinases 1 and 2. It is highly enriched in specific neuronal populations, especially striatal medium-size spiny neurons. As PP1 inhibitor DARPP-32 amplifies and/or mediates many actions of PKA at the plasma membrane and in the cytoplasm, with a broad spectrum of potential targets and functions. DARPP-32 also undergoes a continuous and tightly regulated cytonuclear shuttling. This trafficking is controlled by phosphorylation of Ser-97, which is necessary for nuclear export. When phosphorylated on Thr-34 and dephosphorylated on Ser-97, DARPP-32 can inhibit PP1 in the nucleus and modulate signaling pathways involved in the regulation of chromatin response. Recent work with multiple transgenic and knockout mutant mice has allowed the dissection of DARPP-32 function in striato-nigral and striato-pallidal neurons. It is implicated in the action of therapeutic and abused psychoactive drugs, in prefrontal cortex function, and in sexual behavior. However, the contribution of DARPP-32 in human behavior remains poorly understood. Post-mortem studies in humans suggest possible alterations of DARPP-32 levels in schizophrenia and bipolar disorder. Genetic studies have revealed a polymorphism with possible association with psychological and psychopathological traits. In addition, a short isoform of DARPP-32, t-DARPP, plays a role in cancer, indicating additional signaling properties. Thus, DARPP-32 is a non-essential but tightly regulated signaling hub molecule which may improve the general performance of the neuronal circuits in which it is expressed.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)
Csnk1a1  (casein kinase 1, alpha 1)
Ppp1ca  (protein phosphatase 1 catalytic subunit alpha)
Ppp1cb  (protein phosphatase 1 catalytic subunit beta)
Ppp1cc  (protein phosphatase 1 catalytic subunit gamma)
Ppp1r1b  (protein phosphatase 1, regulatory (inhibitor) subunit 1B)
Ppp2ca  (protein phosphatase 2 catalytic subunit alpha)
Ppp2cb  (protein phosphatase 2 catalytic subunit beta)
Ppp2r3a  (protein phosphatase 2, regulatory subunit B'', alpha)
Ppp2r5d  (protein phosphatase 2, regulatory subunit B', delta)
Ppp3ca  (protein phosphatase 3 catalytic subunit alpha)
Ppp3cb  (protein phosphatase 3 catalytic subunit beta)
Ppp3cc  (protein phosphatase 3 catalytic subunit gamma)
Prkaca  (protein kinase cAMP-activated catalytic subunit alpha)
Prkacb  (protein kinase cAMP-activated catalytic subunit beta)

Genes (Mus musculus)
Cdk5  (cyclin dependent kinase 5)
Csnk1a1  (casein kinase 1, alpha 1)
Ppp1ca  (protein phosphatase 1 catalytic subunit alpha)
Ppp1cb  (protein phosphatase 1 catalytic subunit beta)
Ppp1cc  (protein phosphatase 1 catalytic subunit gamma)
Ppp1r1b  (protein phosphatase 1, regulatory inhibitor subunit 1B)
Ppp2ca  (protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform)
Ppp2cb  (protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform)
Ppp2r3a  (protein phosphatase 2, regulatory subunit B'', alpha)
Ppp2r5d  (protein phosphatase 2, regulatory subunit B', delta)
Ppp3ca  (protein phosphatase 3, catalytic subunit, alpha isoform)
Ppp3cb  (protein phosphatase 3, catalytic subunit, beta isoform)
Ppp3cc  (protein phosphatase 3, catalytic subunit, gamma isoform)
Prkaca  (protein kinase, cAMP dependent, catalytic, alpha)
Prkacb  (protein kinase, cAMP dependent, catalytic, beta)

Genes (Homo sapiens)
CDK5  (cyclin dependent kinase 5)
CSNK1A1  (casein kinase 1 alpha 1)
PPP1CA  (protein phosphatase 1 catalytic subunit alpha)
PPP1CB  (protein phosphatase 1 catalytic subunit beta)
PPP1CC  (protein phosphatase 1 catalytic subunit gamma)
PPP1R1B  (protein phosphatase 1 regulatory inhibitor subunit 1B)
PPP2CA  (protein phosphatase 2 catalytic subunit alpha)
PPP2CB  (protein phosphatase 2 catalytic subunit beta)
PPP2R3A  (protein phosphatase 2 regulatory subunit B''alpha)
PPP2R5D  (protein phosphatase 2 regulatory subunit B'delta)
PPP3CA  (protein phosphatase 3 catalytic subunit alpha)
PPP3CB  (protein phosphatase 3 catalytic subunit beta)
PPP3CC  (protein phosphatase 3 catalytic subunit gamma)
PRKACA  (protein kinase cAMP-activated catalytic subunit alpha)
PRKACB  (protein kinase cAMP-activated catalytic subunit beta)
PRKACG  (protein kinase cAMP-activated catalytic subunit gamma)


Additional Information