Phospholipase Cγ binds α1β1 integrin and modulates α1β1 integrin-specific adhesion

Abstract

Integrin adhesion receptors have been implicated in bidirectional signal transduction. The dynamic regulation of integrin affinity and avidity as well as post-ligand effects involved in outside-in signaling depends on the interaction of integrins with cytoskeletal and signaling proteins. In this study, we attempted to identify cytoplasmic binding partners of α1β1 integrin. We were able to show that cell adhesion to α1β1-specific substrates results in the association of phospholipase Cγ (PLCγ) with the α1β1 integrin independent of PLCγ tyrosine phosphorylation. Using peptide-binding assays, the membrane proximal sequences within the α1β1 integrin subunits were identified as binding sites for PLCγ. In particular, the conserved sequence of β1 subunit binds the enzyme very efficiently. Because purified PLCγ also binds the integrin peptides, binding seems to be direct. Inhibition of PLC by U73122 leads to reduced cell adhesion on α1β1-specific substrates. Cells lacking the conserved domain of the α1 subunit fail to respond to the PLC inhibition, indicating that this domain is necessary for PLC-dependent adhesion modulation of α1β1 integrin.