Phosphorylation of glycogen synthase kinase-3beta at serine-9 by phospholipase Cgamma1 through protein kinase C in rat 3Y1 fibroblasts.
Phospholipase Cgamma1 (PLCgamma1) plays an important role in controlling cellular proliferation and differentiation. PLCgamma1 is overexpressed in some tumors, and its overexpression induces solid tumors in nude mice. However, the regulatory mechanisms underlying PLCgamma1-induced cell proliferation are not fully understood. Here we show that overexpression of PLCgamma1 highly phosphorylated glycogen synthase kinase-3beta (GSK-3beta) at serine-9 in 3Y1 fibroblasts. Inhibition of protein kinase C (PKC)s with GF109203X abrogated GSK-3beta phosphorylation by PLCgamma1. 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 PLCgamma1-transfected cells as compared with vector-transfected cells. Since GSK-3beta is involved in cyclin D1 proteolysis in response to mitogenic stimulation, PLCgamma1-mediated GSK-3beta phosphorylation may function as a regulation of cyclin D1 accumulation in PLCgamma1-overexpressing cells.
Shin
Soon Young
SY
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
Yoon
Se Chang
SC
Kim
Young Ho
YH
Kim
Yong Sik
YS
Lee
Young Han
YH
D000818:Animals; D019938:Cyclin D1 / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008934:Mitogens / Q000494:pharmacology; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D008934:Mitogens; D019938:Cyclin D1; D010768:Phosphoserine; D004815:Epidermal Growth Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; D010738:Type C Phospholipases; D051966:Phospholipase C gamma