Mac-1-dependent tyrosine phosphorylation during neutrophil adhesion

Activated neutrophils display an array of physiological responses, includin g initiation of the oxidative burst, phagocytosis, and cell migration, that are associated with cellular adhesion. Under conditions that lead to cellu lar adhesion, we observed rapid tyrosine phosphorylation of an intracellula r protein with an approximate relative molecular mass of 92 kDa (p92). Phos phorylation of p92 was inducible when Mac-1 was activated by phorbol 12-myr istate 13-acetate, the beta (2)-specific activating antibody CBR LFA-1/2, o r interleukin-8 (77 amino acids). In addition, tyrosine phosphorylation of p92 was dependent on engagement of Mac-1 with ligand. Several observations suggest that this event may be an important step in the signaling pathway i nitiated by Mac-1 binding. p92 phosphorylation was specifically blocked wit h antibodies to CD11b, the alpha -subunit of Mac-1 , and was rapidly revers ible on disengagement of the integrin ligand interaction. Integrin-stimulat ed phosphorylation of p92 created binding sites that were recognized in vit ro by the SH2 domains of c-CrkII and Src. Our observations suggest that neu trophil adhesion mediated through the binding of the beta (2)-integrin Mac- 1 initiates a signaling cascade that involves the activation of protein tyr osine kinases and leads to the regulation of protein-protein interactions v ia SH2 domains, a key process shared with growth factor signaling pathways.