Integrins as Tethering Sensors

Science's STKE  14 Oct 2003:
Vol. 2003, Issue 204, pp. tw403-TW403
DOI: 10.1126/stke.2003.204.tw403

Integrins serve both as adhesion molecules that tether cells to the surface on which they are growing and as signaling receptors that contribute to cell regulation. Precisely how these two roles are coordinated is not clear. There is evidence that clustering of integrins, like that of other receptors, can promote signaling, but the relative importance of clustering, ligand binding, and mechanical tethering remains to be fully explored. Shi and Boettiger analyzed signaling by the integrin α5β1 in a human fibrosarcoma cell line. One consequence of integrin signaling is phosphorylation of the protein kinase FAK (focal adhesion kinase) on multiple sites, and phosphorylation of particular sites depended on the manner in which the integrin molecule was stimulated. The authors compared the results of integrin binding with antibodies or with a fragment of fibronectin that represents the normal ligand for the integrin. They also evaluated the consequences of clustering such complexes by addition of secondary antibodies. Although phosphorylation of FAK on Tyr861 (Y861) was enhanced when bound integrins were clustered, phosphorylation of Tyr397 (Y397) could not be stimulated, in this manner, even by the clustered fibronectin fragment. Phosphorylation of Y397 was only recapitulated when the antibody or ligand to which the integrin bound was itself tethered to the surface of the tissue culture plate. The authors suggest that the integrin α5β1 can thus provide distinct biochemical signals, by reporting both the presence of its ligand and whether that ligand is anchored in such a way that it tethers the cell.

Q. Shi, D. Boettiger, A novel mode for integrin-mediated signaling: Tethering is required for phosphorylation of FAK Y397. Mol. Biol. Cell 14, 4306-4315 (2003). [Abstract] [Full Text]