ERK Pathway Mediates the Activation of Cdk2 in IGF-1–Induced Proliferation of Human Osteosarcoma MG-63 Cells

• DOI: 10.1359/jbmr.1999.14.4.528
• Publication Date: 2006-04-27T01:11:44Z
• Authors: Wenyu Zhang; John C. Lee; Sanjay Kumar; Maxine Gowen
• Keywords: Flavonoids; 0301 basic medicine; Mitogen-Activated Protein Kinase 3; Osteoblasts; Cell Cycle; Cyclin-Dependent Kinase 2; Cyclin A; Kinetin; Protein Serine-Threonine Kinases; Models, Biological; Retinoblastoma Protein; Cyclin-Dependent Kinases; Enzyme Activation; 03 medical and health sciences; Purines; Calcium-Calmodulin-Dependent Protein Kinases; CDC2-CDC28 Kinases; Humans; Insulin-Like Growth Factor I; Mitogen-Activated Protein Kinases; Phosphorylation; Cell Division

Insulin-like growth factor-1 (IGF-1) is a potent mitogen for osteoblasts. The primary signaling mechanism involved in mediating this proliferative effect of IGF-1 not well defined. roles extracellular signal-regulated kinase 1 (ERK1) and cyclin-dependent 2 (Cdk2) kinases the IGF-1-induced pathway human osteosarcoma MG63 cells were investigated using selective inhibitor MEK, PD98059, Cdk inhibitor, olomoucine. Treatment with PD98059 olomoucine inhibited IGF-1-stimulated proliferation these induced cell cycle arrest at G0/G1. significantly abolished activity ERK1 dose-dependent manner. also Cdk2 stimulated cells, although inhibition by was much greater. extent consistent their effects on cycle. Cyclin A complexed unstimulated but complex up-regulated only IGF-1-treated cells. This an observed hyperphosphorylation retinoblastoma protein (pRb) possibility that activated phosphorylation pRb proliferation. Taken together, results suggest MEK/ERK act positive regulatory fashion to activate mitogenesis