Stimulation of tyrosine phosphorylation after ligation of β7 and β1 integrins on human B cells

Abstract

B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to β1 integrins, predominantly α4β1, mature B cells also express α4β7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal addressin cell adhesion molecule- 1. Here we describe that crosslinking of α4β7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105-130 kD, indicating that β7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of α4β1. Interestingly, ligation of α5β1 or α6β1 also stimulated the 105-125 kD group of phosphorylated proteins, whereas ligation of β2 integrins did not. The focal adhesion tyrosine kinase p125(FAK) was identified as one of these substrates, β1 or β7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.