Association of focal adhesion kinase with Grb7 and its role in cell migration.
Focal adhesion kinase (FAK) has been implicated to play a key role in integrin-mediated signal transduction in cell migration. Grb7 is an Src homology (SH) 2-containing and pleckstrin homology domain-containing molecule, which shares significant homology with the Caenorhabditis elegans gene for Mig-10 involved in cell migration during embryogenesis. Here, we report that the SH2 domain of Grb7 can directly interact with FAK through Tyr-397, a major autophosphorylation site in vitro and in vivo. This interaction is cell adhesion-dependent, suggesting that the FAK-Grb7 complex is involved in integrin signaling. Using tetracycline-regulated expression system, we showed that overexpression of Grb7 enhanced cell migration toward fibronectin, whereas overexpression of its SH2 domain alone inhibited cell migration. In addition, we found that phosphorylation of FAK or p130(cas) was not affected by the expression of either Grb7 or its SH2 domain alone, suggesting that Grb7 is downstream of FAK and does not compete with Src for binding to FAK in vivo. Taken together, these results suggest that the FAK-Grb7 complex plays a role in cell migration stimulated by integrin signaling through FAK.
Han
D C
DC
Cancer Biology Laboratories, Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
Guan
J L
JL
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051382:GRB7 Adaptor Protein; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D014162:Transfection; D018909:src Homology Domains
D015815:Cell Adhesion Molecules; C495955:GRB7 protein, human; C495956:Grb7 protein, mouse; D011506:Proteins; D051382:GRB7 Adaptor Protein; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse