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

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 A...

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Published inMolecular biology of the cell Vol. 16; no. 9; pp. 4454 - 4461
Main Authors de Alvaro, Cristina, Martinez, Natalia, Rojas, Jose M, Lorenzo, Margarita
Format Journal Article
LanguageEnglish
Published United States 01.09.2005
Subjects
Adaptor Proteins, Signal Transducing
Amino Acid Substitution
Animals
Cell Differentiation - physiology
Cell Line
Fibroblast Growth Factor 2 - physiology
Humans
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Mice
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Muscle, Skeletal - physiology
Mutation
Myoblasts - cytology
Myoblasts - metabolism
Proteins - genetics
Proteins - metabolism
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Summary: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.
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ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E05-05-0419