Fibronectin type III repeats mediate RGD-independent adhesion and signaling through activated beta 1 integrins

Many cell-surface and extracellular matrix proteins contain multiple modular domains known as fibronectin type III (FNIII) repeats. Cells adhere to the extracellular matrix proteins fibronectin and tenascin in part by the interaction of certain integrins with the Arg-Gly-Asp (RGD) sequence, displayed on specific FNIII repeats, We have found that, after experimental activation of beta 1 integrins, a number of cell types adhere and spread on FNIII repeats lacking RGD, derived from extracellular matrix proteins and cytokine receptors, Interaction between individual FNIII domains and beta 1 integrins mediates focal adhesion kinase phosphorylation and subsequent stress fiber and focal contact formation, These data suggest that many FNIII-containing proteins may bind and signal through activated beta 1 integrins, dramatically expanding the potential for integrin-dependent intercellular and cell-matrix communication.