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© The Rockefeller University Press, 0021-9525/1999//1107 $5.00
The Journal of Cell Biology, Volume 146, Number 5, , 1999 1107-1116

Regulation of Cell Contraction and Membrane Ruffling by Distinct Signals in Migratory Cells

^a Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037
The Scripps Research Institute, Department of Immunology, CAL-9, 10550 N. Torrey Pines Rd., La Jolla, CA 92037.(858) 784-7785(858) 784-7750

klemke{at}scripps.edu

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.

Key Words: adaptor proteins • cell migration • mitogen-activated protein kinase • myosin • signal transduction

© 1999 The Rockefeller University Press

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