Trans-dominant inhibition of integrin function.

F Diaz-Gonzalez, J Forsyth, B Steiner… - Molecular biology of …, 1996 - Am Soc Cell Biol
F Diaz-Gonzalez, J Forsyth, B Steiner, MH Ginsberg
Molecular biology of the cell, 1996Am Soc Cell Biol
Occupancy of integrin adhesion receptors can alter the functions of other integrins and
cause partition of the ligand-occupied integrin into focal adhesions. Ligand binding also
changes the conformation of integrin extracellular domains. To explore the relationship
between ligand-induced conformational change and integrin signaling, we examined the
effect of ligands specific for integrin alpha IIb beta 3 on the functions of target integrins alpha
5 beta 1 and alpha 2 beta 1. We report that binding of integrin-specific ligands to a …
Occupancy of integrin adhesion receptors can alter the functions of other integrins and cause partition of the ligand-occupied integrin into focal adhesions. Ligand binding also changes the conformation of integrin extracellular domains. To explore the relationship between ligand-induced conformational change and integrin signaling, we examined the effect of ligands specific for integrin alpha IIb beta 3 on the functions of target integrins alpha 5 beta 1 and alpha 2 beta 1. We report that binding of integrin-specific ligands to a suppressive integrin can inhibit the function of other target integrins (trans-dominant inhibition). Trans-dominant inhibition is due to a blockade of integrin signaling. Furthermore, this inhibition involves both a conformational change in the extracellular domain and the presence of the beta cytoplasmic tail in the suppressive integrin. Similarly, ligand-induced recruitment of alpha IIb beta 3 to focal adhesions also involves a conformational rearrangement of its extracellular domain. These findings imply that the ligand-induced conformational changes can propagate from an integrin's extracellular to its intracellular face. Trans-dominant inhibition by integrin ligands may coordinate integrin signaling and can lead to unexpected biological effects of integrin-specific inhibitors.
Am Soc Cell Biol