Integrin cytoplasmic domains mediate inside-out signal transduction

Abstract

We analyzed the binding of fibronectin to integrin α5β1 in various cells; in some cells fibronectin bound with low affinity (e.g., K562 cells) whereas in others (e.g., CHO), it bound with high affinity (Kd ~ 100 nM) in an energy-dependent manner. We constructed chimeras of the extracellular and transmembrane domains of α(IIb)β3 joined to the cytoplasmic domains of α5β1. The affinity state of these chimeras was assessed by binding of fibrinogen or the monoclonal antibody, PAC1. The cytoplasmic domains of α5β1 conferred an energy-dependent high affinity state on α(IIb)β3 in CHO but not K562 cells. Three additional α cytoplasmic domains (α2, α6A, α6B) conferred PAC1 binding in CHO cells, while ..