Sprouty-2 Overexpression in C2C12 Cells Confers Myogenic Differentiation Properties in the Presence of FGF2
Open Access
- 1 September 2005
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 16 (9), 4454-4461
- https://doi.org/10.1091/mbc.e05-05-0419
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 p21CIP) 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.Keywords
This publication has 43 references indexed in Scilit:
- Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-kinase-dependent, -β-catenin-independent signaling pathwayExperimental Cell Research, 2004
- Tyrosine Phosphorylation of Sprouty Proteins Regulates Their Ability to Inhibit Growth Factor Signaling: A Dual Feedback LoopMolecular Biology of the Cell, 2004
- Activation of the ERK1/2 and p38 Mitogen-activated Protein Kinase Pathways Mediates Fibroblast Growth Factor-induced Growth Arrest of ChondrocytesJournal of Biological Chemistry, 2004
- IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrientsThe Journal of cell biology, 2003
- Regulation of insulin-like growth factor–dependent myoblast differentiation by Foxo forkhead transcription factorsThe Journal of cell biology, 2003
- Differential effects of Ras signaling through NFκB on skeletal myogenesisOncogene, 2001
- Insulin signaling leading to proliferation, survival, and membrane ruffling in C2C12 myoblastsJournal of Cellular Physiology, 2001
- Insulin produces myogenesis in C2C12 myoblasts by induction of NF-?B and downregulation of AP-1 activitiesJournal of Cellular Physiology, 2000
- Induction of Akt-2 Correlates with Differentiation in Sol8 Muscle CellsBiochemical and Biophysical Research Communications, 1998
- The Mitogenic and Myogenic Actions of Insulin-like Growth Factors Utilize Distinct Signaling PathwaysPublished by Elsevier BV ,1997