Role of the cytoplasmic tyrosines of beta 1A integrins in transformation by v-src

CD25 cells lacking pi integrins or expressing beta 1A with mutations of con served cytoplasmic tyrosines (Y783, Y795) to phenylalanine have poor direct ed migration to platelet-derived growth factor or lysophosphatidic acid whe n compared with GD25 cells expressing wild-type beta 1A, We studied the eff ects of v-src on these cells. Transformation with v-src caused tyrosine and serine phosphorylation of wild-type beta 1A but not of Y783/795F doubly mu tated beta 1A, v-src-transformed cells had rounded and/or fusiform morpholo gy and poor assembly of fibronectin matrix. Adhesion to fibronectin or lami nin and coupling of focal contacts to actin-containing cytoskeleton were pr eserved in transformed Y783/795F cells but lost on transformation when beta 1A was wild type. Transformed Y783/795F cells also retained ability, albei t limited, to migrate across filters, whereas transformed cells with wild-t ype beta 1A were unable to transverse filters. Studies of single tyrosine m utants showed that the more important tyrosine for retaining ability to adh ere, assemble focal contacts, and migrate is Y783. These results suggest th at overactive phosphorylation of cytoplasmic residues of beta 1A, particula rly Y783, accounts in part for the phenotype of v-src-transformed cells.