BETA-2 INTEGRIN-DEPENDENT TYROSINE PHOSPHORYLATION OF PAXILLIN IN HUMAN NEUTROPHILS TREATED WITH TUMOR-NECROSIS-FACTOR

The focal adhesion protein paxillin undergoes tyrosine phosphorylation in response to signals mediated by integrins, neuropeptides and oncog ene products, possibly via activation of the focal adhesion-associated kinase, p125(FAK). In the present work, tumor necrosis factor-alpha ( TNF) stimulated tyrosine phosphorylation of paxillin in human neutroph ils. Cell adhesion and participation of the beta 2 integrin CD18 were necessary, but not sufficient, for the response. Adherent neutrophils also tyrosine phosphorylated paxillin in response to phorbol ester, fo rmylmethionyl-leucyl-phenylalanine and opsonized bacteria. In contrast , p125(FAK) was constitutively tyrosine phosphorylated in a manner una ffected by adherence and/or TNF. Thus, cytokines and microbial product s are among the stimuli that can induce the tyrosine phosphorylation o f paxillin, and kinases other than p125(FAK) may be responsible. This is the first identification of paxillin and p125(FAK) in human cells a nd neutrophils, and one of the few identifications of a specific prote in that undergoes tyrosine phosphorylation in response to any agonist in neutrophils or in response to TNF in any cell.