Phosphorylation of glycogen synthase kinase-3β at serine-9 by phospholipase Cγ1 through protein kinase C in rat 3Y1 fibroblasts

Abstract

Phospholipase Cγ1 (PLCγ1) plays an important role in controlling cellular proliferation and differentiation. PLCγ1 is overexpressed in some tumors, and its overexpression induces solid tumors in nude mice. However, the regulatory mechanisms underlying PLCγ1-induced cell proliferation are not fully understood. Here we show that overexpression of PLCγ1 highly phosphorylated glycogen synthase kinase-3β (GSK-3β) at serine-9 in 3Y1 fibroblasts. Inhibition of protein kinase C (PKC)s with GF109203X abrogated GSK-3β phosphorylation by PLCγ1. We also found that steady-state level of cyclin D1 protein, but not cyclin D1 mRNA, was highly elevated in response to serum stimulation in PLCγ1-transfected cells as compared with vector-transfected cells. Since GSK-3β is involved in cyclin D1 proteolysis in response to mitogenic stimulation, PLCγ1-mediated GSK-3β phosphorylation may function as a regulation of cyclin D1 accumulation in PLCγ1-overexpressing cells.