Integrin Signals Specified from Without

Abstract

Integrins are receptors that interact with the extracellular matix and transmit signals into the cytoplasm. Integrin signals lead to activation of the small guanosine triphosphatases Cdc42, Rac, and Rho. Miao et al. used overexpression of integrin β3 subunits in Chinese hamster ovary cells to show that β3 integrin is coupled to activation of Rho and formation of stress fibers, whereas activation of β1 integrin is coupled to activation of Rac and formation of lamellipodia. The specificity of ligand binding of β integrin subunits is determined by an extracellular region known as the I domain. Replacement of the I domain of β1 integrin with the I domain from β3 integrin caused the resulting chimeric integrin to have ligand-binding specificity of β3 integrin and to couple to activation of Rho rather than Rac. The results indicate that β1 and β3 integrins are coupled to distinct signaling outputs. And, it appears that, depending on which extracellular I domain is present, ligand binding may cause distinct conformational changes in the β subunit that lead to coupling of the intracellular portion of the receptor to alternate signaling partners. H. Miao, S. Li, Y.-L. Hu, S. Yuan, Y. Zhao, B. P. C. Chen, W. Puzon-McLaughlin, T. Tarui, J. Y.-J. Shyy, Y. Takada, S. Usami, S. Chien, Differential regulation of Rho GTPases by β1 and β3 integrins: The role of an extracellular domain of integrin in intracellular signaling. J. Cell Sci. 115 , 2199-2206 (2002). [Online Journal]