Specific changes in rasGAP-associated 62 kilodalton protein during integrin mediated cell-substrate interaction.
A cascade of signal transduction events is initiated when cells make contact with each other or with a substrate. The nature of these signal transduction pathways is beginning to be elucidated. In particular, adhesive interactions between cells and their substrate, mediated by cell-surface integrins and extracellular matrix proteins, appears to activate the MAP kinase pathway. Here we show that in mouse fibroblasts and rat epithelial cells, tyrosine phosphorylation of a 62 kilodalton rasGAP-associated protein (GAPa-p62) is decreased upon cell-substrate interaction. Interaction between fibroblasts and various extracellular matrices such as fibronectin, vitronectin and collagen IV, but not laminin, results in tyrosine dephosphorylation of GAPa-p62. Cell-substrate mediated tyrosine dephosphorylation of GAPa-p62 is defective in transformed cell lines, suggesting a possible role for p62 in tumorigenic transformation. These studies suggest that in fibroblasts, and perhaps even in epithelial cells, the signal transduction pathway(s) triggered by different integrin engagement events converge on the rasGAP protein and alter the tyrosine phosphorylation and/or association of GAPa-p62.
Sharma
S V
SV
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163, USA.
Boyajian
A
A
Myers
C D
CD
Nakano
H
H
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D011905:Genes, ras; D016391:Genes, src; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D014443:Tyrosine / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D005353:Fibronectins; D020690:GTPase-Activating Proteins; D016023:Integrins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine