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Phosphorylation of pRb is required for HGF‐induced muscle cell proliferation and is p27 kip1 ‐dependent
Author(s) -
Leshem Yael,
Halevy Orna
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10089
Subject(s) - retinoblastoma protein , hepatocyte growth factor , transactivation , cell cycle , ectopic expression , microbiology and biotechnology , phosphorylation , biology , mef2 , cyclin dependent kinase , e2f1 , cell growth , hyperphosphorylation , cancer research , transcription factor , chemistry , cell , cell culture , biochemistry , genetics , receptor , enhancer , gene
Hepatocyte growth factor (HGF) plays a crucial role in the differentiation of skeletal muscle cells, where a process in which the retinoblastoma protein (pRb) has been implicated. We addressed the role of pRb in HGF‐mediated effects on the proliferation and differentiation of adult skeletal muscle myoblasts. HGF shifted pRb to its hyperphosphorylation forms and increased the transactivation of E2F1, a transcription factor required for S phase entry. A constitutively active pRb mutant blocked HGF‐dependent pRb phosphorylation and transactivation of E2F1 and increased cell proliferation. Accordingly, this mutant reversed the inhibitory effects of HGF on the expression of the cyclin‐dependent kinase (CDK) inhibitor p27 and myogenic differentiation markers. HGF‐mediated pRb phosphorylation was reversed by ectopic expression of p27, but neither the myogenic regulatory factor, MEF2, nor the myogenic inhibitory protein Twist had that effect. These results suggest that in response to HGF signaling, there is a decrease in p27 expression that results in an accumulation of hyperphosphorylated Rb protein, and subsequent progression of myoblasts into the G 1 phase of the cell cycle. J. Cell. Physiol. 191: 173–182, 2002. © 2002 Wiley‐Liss, Inc.