Focal Adhesion Kinase-Related fakB Is Regulated by the Integrin LFA-1and Interacts with the SH3 Domain of Phospholipase Cγ1

Signal transduction through integrin molecules expressed on platelets and nonlymphoid cells involves activation of the intracellular focal adhesion kinase pp125FAK(FAK) to phosphorylate substrate proteins on tyrosine residues. Similar mechanisms are also functional in T-lymphocytes through the β1-integrin VLA-4. A putative FAK-related phosphoprotein (fakB) was identified that is responsive to intracellular signals induced through ligation of antigen receptors on both T- and B-lymphocytes, and whose induced tyrosine phosphorylation is augmented by TCR costimulation through the adhesion/costimulatory receptors CD2 and CD4. In this report, fakB is shown to respond to extracellular signals through the β2-integrin LFA-1 in the absence of primary signals through the TCR. Protein–protein complex formation was observed involving an association between fakB, phospholipase Cγ1 (PLCγ1), and the tyrosine phosphoprotein pp35-36. Evidence is provided here that fakB interacts with PLCγ1 through its SH3 domain. The association between fakB and PLCγ1 does not appear to require T-cell activation, whereas the induced tyrosine phosphorylation of the protein complex components occurs following engagement of LFA-1. These data indicate that the β2-integrin LFA-1 expressed on T-lymphocytes stimulates a novel FAK-related molecule that may function in the interplay between adhesion receptors and intracellular signaling enzymes responsible for downstream second messenger generation.