beta 2 integrin-dependent phosphorylation of protein-tyrosine kinase Pyk2 stimulated by tumor necrosis factor alpha and fMLP in human neutrophils adherent to fibrinogen

Tumor necrosis factor alpha and fMLP can activate a broad range of cellular functions in neutrophils adherent to biological surfaces. These functions are mediated by integrins and involve the activation of tyrosine kinases. H ere, we report that Pyk2, a member of the focal adhesion kinase family, was present in human neutrophils and was rapidly phosphorylated and activated following tumor necrosis factor a and fMLP stimulation in an adhesion-depen dent manner. Tyrosine phosphorylation of Pyk2 was attenuated by beta(2) int egrin blocking with specific antibodies. The tyrosine phosphorylation of Py k2 was downstream of protein kinases Lyn, Syk and protein kinase C and cyto skeletal organization. The activation of Pyk2 may play a role in adhesion/c ytoskeleton-associated neutrophils function. (C) 1999 Federation of Europea n Biochemical Societies.