RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages.
Copyright policy )RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages.
Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of alphav/beta3-integrin-mediated cell-matrix connections requires the receptor-like tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alphav-integrins at the leading edge during early spreading, and coimmunoprecipitates with alphav-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening of alphav/beta3-integrin-cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPalpha is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.
- New York University School of Medicine United States
- Department of Biological Sciences Columbia University United States
- University of Copenhagen Denmark
- Columbia University United States
- Columbia University United States
Mice, Knockout, Focal Adhesions, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Cell Membrane, Fluorescent Antibody Technique, Receptors, Cell Surface, Fibroblasts, Integrin alphaVbeta3, Proto-Oncogene Proteins c-fyn, Extracellular Matrix, Fibronectins, Mice, Cell Movement, Proto-Oncogene Proteins, Cell Adhesion, Animals, Protein Tyrosine Phosphatases, Cells, Cultured, Cytoskeleton, Signal Transduction
Mice, Knockout, Focal Adhesions, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Cell Membrane, Fluorescent Antibody Technique, Receptors, Cell Surface, Fibroblasts, Integrin alphaVbeta3, Proto-Oncogene Proteins c-fyn, Extracellular Matrix, Fibronectins, Mice, Cell Movement, Proto-Oncogene Proteins, Cell Adhesion, Animals, Protein Tyrosine Phosphatases, Cells, Cultured, Cytoskeleton, Signal Transduction
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