RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages.
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Cell Biology |
Volume | 161 |
Issue number | 1 |
Pages (from-to) | 143-53 |
Number of pages | 10 |
ISSN | 0021-9525 |
DOIs | |
Publication status | Published - 2003 |
Bibliographical note
Keywords: Animals; Cell Adhesion; Cell Membrane; Cell Movement; Cells, Cultured; Cytoskeleton; Extracellular Matrix; Fibroblasts; Fibronectins; Fluorescent Antibody Technique; Focal Adhesions; Integrin alphaVbeta3; Mice; Mice, Knockout; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fyn; Receptor-Like Protein Tyrosine Phosphatases, Class 4; Receptors, Cell Surface; Signal Transduction; Stress, Mechanical; Vimentin; src-Family Kinases
ID: 5069601