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/
) is a convergent downstream target of the insulin-stimulated phosphatidylinositol 3-kinase and TC10 signaling pathways
Address correspondence to Jeffrey E. Pessin, Dept. of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794-8651. Tel.: (631) 444-3083. Fax: (631) 444-3022. email: pessin{at}pharm.sunysb.edu
Insulin stimulation of adipocytes resulted in the recruitment of atypical PKC (PKC
/
) to plasma membrane lipid raft microdomains. This redistribution of PKC/ was prevented by Clostridium difficile toxin B and by cholesterol depletion, but was unaffected by inhibition of phosphatidylinositol (PI) 3-kinase activity. Expression of the constitutively active GTP-bound form of TC10 (TC10Q/75L), but not the inactive GDP-bound mutant (TC10/T31N), targeted PKC/ to the plasma membrane through an indirect association with the Par6–Par3 protein complex. In parallel, insulin stimulation as well as TC10/Q75L resulted in the activation loop phosphorylation of PKC. Although PI 3-kinase activation also resulted in PKC/ phosphorylation, it was not recruited to the plasma membrane. Furthermore, insulin-induced GSK-3ß phosphorylation was mediated by both PI 3-kinase–PKB and the TC10–Par6–atypical PKC signaling pathways. Together, these data demonstrate that PKC/ can serve as a convergent downstream target for both the PI 3-kinase and TC10 signaling pathways, but only the TC10 pathway induces a spatially restricted targeting to the plasma membrane.
Key Words: insulin; signal transduction; adipocyte; lipid raft; compartmentalization
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