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As a major target for
dopamine-activated adenylyl cyclase and protein kinase A in the
striatum, DARPP-32 plays a central role in regulating the efficacy
of dopaminergic neurotransmission and can act either as a
phosphatase or kinase inhibitor in a contextually dependent manner.
Growing evidence points to DARPP-32 as a key mediator/modulator in
numerous signal transduction cascades implicated in a growing number
of neurological disorders such as schizophrenia and depression, as
well as in drug abuse and addiction. For example, it has been shown
that acute exposure of mice to cocaine increases phosphorylation of
DARPP-32 at Thr34 with a concommitment decrease in phosphorylation at
Thr75, whereas chronic exposure leads to a reversal of this phospho
profile. It has also been observed that many schizophrenic patients
show decreased levels of DARPP-32 in the prefrontal cortex.
While the precise role that DARPP-32
plays in these psychiatric disorders is still being elucidated, the
existing body of literature clearly portrays DARPP-32 as playing a
central role in multiple signaling pathways. Further research will
determine neuronal subpopulations where phosphorylation of
DARPP-32 occurs as well as the functional importance of previously
identified phospho sites of DARPP-32.
IMGENEX offers over one-thousand
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DARPP-32: Central regulatory protein in multiple
signaling pathways.
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