Sprouty-2 overexpression in C2C12 cells confers myogenic differentiation properties in the presence of FGF2.

Abstract:

:Myoblast C2C12 cells cultured in the presence of FGF2 actively proliferate and showed a differentiation-defective phenotype compared with cells cultured in low serum or in the presence of insulin. These FGF2 effects are associated with sustained activation of p44/p42-MAPK and lack of activation of AKT. Here we demonstrate that Sprouty-2, a protein involved in the negative feedback of receptor tyrosine kinase signaling, when stably overexpressed in C2C12 cells and in the presence of FGF2 produces growth arrest (precluding the expression of PCNA and the phosphorylation of retinoblastoma and inducing the expression of p21(CIP)) and myogenesis (multinucleated myotubes formation, induction of creatine kinase and expression of myosin heavy chain protein). These events were accompanied by repression of p44/p42-MAPK and activation of AKT. When C2C12 cells were stably transfected with a Sprouty-2 (Y55F) mutant defective in inhibiting p44/p42-MAPK activation by FGF, myoblasts in the presence of FGF continue to grow and completely fail to form myotubes. This work is the first evidence of the contribution of sprouty genes to myogenic differentiation in the presence of FGF2.

journal_name

Mol Biol Cell

authors

de Alvaro C,Martinez N,Rojas JM,Lorenzo M

doi

10.1091/mbc.e05-05-0419

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

4454-61

issue

9

eissn

1059-1524

issn

1939-4586

pii

E05-05-0419

journal_volume

16

pub_type

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