Exp Mol Med.
2002 Dec;34(6):444-450.
Phosphorylation of glycogen synthase kinase-3beta at serine-9 by phospholipase Cgamma1 through protein kinase C in rat 3Y1 fibroblasts
- Affiliations
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- 1Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea. younglee@med.yu.ac.kr
- 2Department of Microbiology, Kyungpook National University, Daegu, Korea.
- 3Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Korea.
- 4Neuroscience Research Institute, SNU-MRC and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Abstract
- 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.
MeSH Terms
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Animals
Cyclin D1/metabolism
Epidermal Growth Factor/pharmacology
Fibroblasts
Gene Expression
Glycogen Synthase Kinase 3/chemistry/*metabolism
Mitogens/pharmacology
Phospholipase C/genetics/*metabolism
Phosphorylation/drug effects
Phosphoserine/*metabolism
Protein Kinase C/antagonists & inhibitors/*metabolism
Rats
Signal Transduction
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