Document Detail

Hepatocyte growth factor (HGF) signals through SHP2 to regulate primary mouse myoblast proliferation.
MedLine Citation:
PMID:  19393645     Owner:  NLM     Status:  MEDLINE    
Niche localized HGF plays an integral role in G(0) exit and the return to mitotic activity of adult skeletal muscle satellite cells. HGF actions are regulated by MET initiated intracellular signaling events that include recruitment of SHP2, a protein tyrosine phosphatase. The importance of SHP2 in HGF-mediated signaling was examined in myoblasts and primary cultures of satellite cells. Myoblasts stably expressing SHP2 (23A2-SHP2) demonstrate increased proliferation rates by comparison to controls or myoblasts expressing a phosphatase-deficient SHP2 (23A2-SHP2DN). By comparison to 23A2 myoblasts, treatment of 23A2-SHP2 cells with HGF does not further increase proliferation rates and 23A2-SHP2DN myoblasts are unresponsive to HGF. Importantly, the effects of SHP2 are independent of downstream ERK1/2 activity as inclusion of PD98059 does not blunt the HGF-induced proliferative response. SHP2 function was further evaluated in primary satellite cell cultures. Ectopic expression of SHP2 in satellite cells tends to decrease proliferation rates and siSHP2 causes an increase the percentage of dividing myogenic cells. Interestingly, treatment of satellite cells with high concentrations of HGF (50 ng/ml) inhibits proliferation, which can be overcome by knockdown of SHP2. From these results, we conclude that HGF signals through SHP2 in myoblasts and satellite cells to directly alter proliferation rates.
Ju Li; Sarah A Reed; Sally E Johnson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-04-23
Journal Detail:
Title:  Experimental cell research     Volume:  315     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-15     Completed Date:  2009-07-20     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2284-92     Citation Subset:  IM    
University of Florida, Department of Animal Sciences, PO Box 110910, Gainesville, FL 32611, USA.
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MeSH Terms
Cell Proliferation*
Cells, Cultured
Hepatocyte Growth Factor / metabolism*
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Myoblasts / cytology,  physiology*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics,  metabolism*
Satellite Cells, Skeletal Muscle / cytology,  physiology
Signal Transduction / physiology*
Grant Support
Reg. No./Substance:
67256-21-7/Hepatocyte Growth Factor; EC Protein Kinase 1; EC Protein Kinase 3; EC Tyrosine Phosphatase, Non-Receptor Type 11; EC protein, mouse

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