Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells.
Cell migration and wound contraction requires assembly of actin into a functional myosin motor unit capable of generating force. However, cell migration also involves formation of actin-containing membrane ruffles. Evidence is provided that actin-myosin assembly and membrane ruffling are regulated by distinct signaling pathways in the migratory cell. Interaction of cells with extracellular matrix proteins or cytokines promote cell migration through activation of the MAP kinases ERK1 and ERK2 as well as the molecular coupling of the adaptor proteins p130CAS and c-CrkII. ERK signaling is independent of CAS/Crk coupling and regulates myosin light chain phosphorylation leading to actin-myosin assembly during cell migration and cell-mediated contraction of a collagen matrix. In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180. Thus, during cell migration ERK and CAS/Crk coupling operate as components of distinct signaling pathways that control actin assembly into myosin motors and membrane ruffles, respectively.
Cheresh
D A
DA
Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Leng
J
J
Klemke
R L
RL
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction / Q000187:drug effects; D020744:rac GTP-Binding Proteins
D000199:Actins; C099818:DOCK1 protein, human; D016326:Extracellular Matrix Proteins; D007328:Insulin; D020409:Molecular Motor Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins; D009218:Myosins; D020744:rac GTP-Binding Proteins