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© The Rockefeller University Press, 0021-9525/2000//457 $5.00
The Journal of Cell Biology, Volume 149, Number 2, , 2000 457-470

Original Article

Role of P120 Ras-Gap in Directed Cell Movement



Sarang V. Kulkarnia, Gerald Gisha, Peter van der Geera, Mark Henkemeyera, and Tony Pawsona

a Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5.(416) 586-8869(416) 586-8262

pawson{at}mshri.on.ca

We have used cell lines deficient in p120 Ras GTPase activating protein (Ras-GAP) to investigate the roles of Ras-GAP and the associated p190 Rho-GAP (p190) in cell polarity and cell migration. Cell wounding assays showed that Ras-GAP–deficient cells were incapable of establishing complete cell polarity and migration into the wound. Stimulation of mutant cells with growth factor rescued defects in cell spreading, Golgi apparatus fragmentation, and polarized vesicular transport and partially rescued migration in a Ras-dependent manner. However, for directional movement, the turnover of stress fibers and focal adhesions to produce an elongate morphology was dependent on the constitutive association between Ras-GAP and p190, independent of Ras regulation. Disruption of the phosphotyrosine-mediated Ras-GAP/p190 complex by microinjecting synthetic peptides derived from p190 sequences in wild-type cells caused a suppression of actin filament reorientation and migration. From these observations we suggest that although Ras-GAP is not directly required for motility per se, it is important for cell polarization by regulating actin stress fiber and focal adhesion reorientation when complexed with 190. This observation suggests a specific function for Ras-GAP separate from Ras regulation in cell motility.

Key Words: cytoskeleton • cell polarity • migration • actin • p190 Rho-GAP

© 2000 The Rockefeller University Press

Dr. van der Geer's present address is University of California at San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0601.

Dr. Henkemeyer's present address is University of Texas, South Western Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75235-9133.

Abbreviations used in this paper: aa, amino acid; FA, focal adhesion; GA, Golgi apparatus; GAPs, GTPase-activating proteins; MT, microtubule; pTyr, phosphotyrosine; SF, stress fiber; VSV, vesicular stomatitis virus.


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