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Phosphatidylinositide 3‐kinase and protein kinase C zeta mediate retinoic acid induction of DARPP‐32 in medium size spiny neurons in vitro
Author(s) -
Pedrini Steve,
Bogush Alexey,
Ehrlich Michelle E
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05475.x
Subject(s) - protein kinase c , map2k7 , biology , protein kinase a , microbiology and biotechnology , medium spiny neuron , signal transduction , cyclin dependent kinase 4 , map kinase kinase kinase , retinoic acid , cyclin dependent kinase 9 , mitogen activated protein kinase kinase , ask1 , cyclin dependent kinase 2 , kinase , biochemistry , endocrinology , dopamine , gene , striatum
Mature striatal medium size spiny neurons express the dopamine and cAMP‐regulated phosphoprotein, 32 kDa (DARPP‐32), but little is known about the mechanisms regulating its levels, or the specification of fully differentiated neuronal subtypes. Cell extrinsic molecules that increase DARPP‐32 mRNA and/or protein levels include retinoic acid (RA), brain‐derived neurotrophic factor, and estrogen (E 2 ). We now demonstrate that RA regulates DARPP‐32 mRNA and protein in primary striatal neuronal cultures. Furthermore, DARPP‐32 induction by RA in vitro requires phosphatidylinositide 3‐kinase, but is independent of tropomyosin‐related kinase B, cyclin‐dependent kinase 5, and protein kinase B. Using pharmacologic inhibitors of various isoforms of protein kinase C (PKC), we also demonstrate that DARPP‐32 induction by RA in vitro is dependent on PKC zeta (PKCζ). Thus, the signal transduction pathways mediated by RA are very different than those mediating DARPP‐32 induction by brain‐derived neurotrophic factor. These data support the presence of multiple signal transduction pathways mediating expression of DARPP‐32 in vitro , including a novel, important pathway via which phosphatidylinositide 3‐kinase regulates the contribution of PKCζ.