The LIM protein Ajuba influences p130Cas localization and Rac1 activity during cell migration.
Cell migration requires extension of lamellipodia that are stabilized by formation of adhesive complexes at the leading edge. Both processes are regulated by signaling proteins recruited to nascent adhesive sites that lead to activation of Rho GTPases. The Ajuba/Zyxin family of LIM proteins are components of cellular adhesive complexes. We show that cells from Ajuba null mice are inhibited in their migration, without associated abnormality in adhesion to extracellular matrix proteins, cell spreading, or integrin activation. Lamellipodia production, or function, is defective and there is a selective reduction in the level and tyrosine phosphorylation of FAK, p130Cas, Crk, and Dock180 at nascent focal complexes. In response to migratory cues Rac activation is blunted in Ajuba null cells, as detected biochemically and by FRET analysis. Ajuba associates with the focal adhesion-targeting domain of p130Cas, and rescue experiments suggest that Ajuba acts upstream of p130Cas to localize p130Cas to nascent adhesive sites in migrating cells thereby leading to the activation of Rac.
Pratt
Stephen J
SJ
Department of Medicine, Washington University, St. Louis, MO 63130, USA.
Epple
Holly
H
Ward
Michael
M
Feng
Yunfeng
Y
Braga
Vania M
VM
Longmore
Gregory D
GD
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018398:Homeodomain Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins; D051379:Mice; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D013997:Time Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; C496062:Pxn protein, mouse; D050717:Retinoblastoma-Like Protein p130; C485607:ajuba protein, mouse; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020830:rac1 GTP-Binding Protein
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