TY - JOUR
T1 - Phosphorylation of pRb is required for HGF-induced muscle cell proliferation and is p27kip1-dependent
AU - Leshem, Yael
AU - Halevy, Orna
PY - 2002
Y1 - 2002
N2 - 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 G1 phase of the cell cycle.
AB - 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 G1 phase of the cell cycle.
UR - http://www.scopus.com/inward/record.url?scp=0036203894&partnerID=8YFLogxK
U2 - 10.1002/jcp.10089
DO - 10.1002/jcp.10089
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C2 - 12064460
AN - SCOPUS:0036203894
SN - 0021-9541
VL - 191
SP - 173
EP - 182
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 2
ER -