Selective regulation of integrin--cytoskeleton interactions by the tyrosine kinase Src.
Cell motility on extracellular-matrix (ECM) substrates depends on the regulated generation of force against the substrate through adhesion receptors known as integrins. Here we show that integrin-mediated traction forces can be selectively modulated by the tyrosine kinase Src. In Src-deficient fibroblasts, cell spreading on the ECM component vitronectin is inhibited, while the strengthening of linkages between integrin vitronectin receptors and the force-generating cytoskeleton in response to substrate rigidity is dramatically increased. In contrast, Src deficiency has no detectable effects on fibronectin-receptor function. Finally, truncated Src (lacking the kinase domain) co-localizes to focal-adhesion sites with alpha v but not with beta 1 integrins. These data are consistent with a selective, functional interaction between Src and the vitronectin receptor that acts at the integrin-cytoskeleton interface to regulate cell spreading and migration.
Felsenfeld
D P
DP
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Schwartzberg
P L
PL
Venegas
A
A
Tse
R
R
Sheetz
M P
MP
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D049452:Green Fluorescent Proteins; D039564:Integrin alphaV; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017469:Receptors, Fibronectin / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D039564:Integrin alphaV; D019012:Integrin beta1; D016023:Integrins; D008164:Luminescent Proteins; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; D049452:Green Fluorescent Proteins; D019061:src-Family Kinases