Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for EGF-induced actin disassembly in C3H10T1/2 fibroblasts.
p190 RhoGAP is a tyrosine phosphorylated protein that contains an N-terminal GTP binding domain, a middle domain (MD) that mediates interaction with p120 RasGAP and a C-terminal GTPase-activating protein (GAP) domain that is specific for the &Rgr; family of small GTPases. Evidence is accumulating to suggest that p190 participates in actin cytoskeleton rearrangements that occur following transformation by v-Src or stimulation by growth factors, and that tyrosine phosphorylation of p190 by Src influences these processes. The current study was performed to establish whether p190RhoGAP directly participates in epidermal growth factor-induced actin stress fiber disassembly and how c-Src is involved in this process. Our results support a model in which the p190 MD negatively regulates the activity of the GAP domain and that c-Src phosphorylation of Y1105 is necessary, but insufficient on its own, for actin stress fiber disassembly.
Haskell
M D
MD
Department of Microbiology and Cancer Center, Box 800734, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Nickles
A L
AL
Agati
J M
JM
Su
L
L
Dukes
B D
BD
Parsons
S J
SJ
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008845:Microinjections; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D014443:Tyrosine / Q000378:metabolism*
D000199:Actins; C513041:Arhgap35 protein, mouse; C513042:Arhgap5 protein, mouse; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase; D016392:Proto-Oncogene Proteins pp60(c-src)