Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis

Sordella, R., Jiang, W., Chen, G. C., Curto, M., Settleman, J. (2003) Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis. Cell, 113 (2). pp. 147-58. ISSN 0092-8674 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/12705864
DOI: 10.1016/S0092-8674(03)00271-X

Abstract

Mature adipocytes and myocytes are derived from a common mesenchymal precursor. While IGF-1 promotes the differentiation of both cell types, the signaling pathways that specify the distinct cell fates are largely unknown. Here, we show that the Rho GTPase and its regulator, p190-B RhoGAP, are components of a critical switch in the adipogenesis-myogenesis "decision." Cells derived from embryos lacking p190-B RhoGAP exhibit excessive Rho activity, are defective for adipogenesis, but undergo myogenesis in response to IGF-1 exposure. In vitro, activation of Rho-kinase by Rho inhibits adipogenesis and is required for myogenesis. The activation state of Rho following IGF-1 signaling is determined by the tyrosine-phosphorylation status of p190-B RhoGAP and its resulting subcellular relocalization. Moreover, adjusting Rho activity is sufficient to alter the differentiation program of adipocyte and myocyte precursors. Together, these results identify the Rho GTPase as an essential modulator of IGF-1 signals that direct the adipogenesis-myogenesis cell fate decision.

Item Type: Paper
Uncontrolled Keywords: Adipose Tissue cytology embryology enzymology Animals Cell Compartmentation drug effects physiology Cell Differentiation drug effects physiology Cells, Cultured DNA-Binding Proteins Dexamethasone/pharmacology Enzyme Inhibitors/pharmacology Fetus GTPase-Activating Proteins Guanine Nucleotide Exchange Factors deficiency genetics Insulin-Like Growth Factor I metabolism pharmacology Mesoderm cytology enzymology Mice Mice, Knockout Muscle Skeletal cytology embryology enzymology Mutation genetics Nuclear Proteins deficiency genetics Protein Transport drug effects physiology Receptor IGF Type 1 genetics metabolism Repressor Proteins Signal Transduction drug effects physiology Stem Cells cytology drug effects enzymology rho GTP-Binding Proteins genetics metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell regulation
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell signaling
CSHL Authors:
Communities: CSHL labs > Sordella lab
Depositing User: CSHL Librarian
Date Deposited: 09 May 2012 17:57
Last Modified: 13 Mar 2013 16:11
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26245

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