title: Mac-1-dependent tyrosine phosphorylation during neutrophil adhesion.
abstract: Activated neutrophils display an array of physiological responses, including initiation of the oxidative burst, phagocytosis, and cell migration, that are associated with cellular adhesion. Under conditions that lead to cellular adhesion, we observed rapid tyrosine phosphorylation of an intracellular protein with an approximate relative molecular mass of 92 kDa (p92). Phosphorylation of p92 was inducible when Mac-1 was activated by phorbol 12-myristate 13-acetate, the beta(2)-specific activating antibody CBR LFA-1/2, or 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 initiated by Mac-1 binding. p92 phosphorylation was specifically blocked with antibodies to CD11b, the alpha-subunit of Mac-1, and was rapidly reversible on disengagement of the integrin ligand interaction. Integrin-stimulated phosphorylation of p92 created binding sites that were recognized in vitro by the SH2 domains of c-CrkII and Src. Our observations suggest that neutrophil adhesion mediated through the binding of the beta(2)-integrin Mac-1 initiates a signaling cascade that involves the activation of protein tyrosine kinases and leads to the regulation of protein-protein interactions via SH2 domains, a key process shared with growth factor signaling pathways.
authors: Department of Internal Medicine, University of Michigan Medical Center and Department of Veterans Affairs Medical Center, Ann Arbor 48109, USA.
authors: M
authors: M
authors: Takami
authors: R
authors: R
authors: Herrera
authors: L
authors: L
authors: Petruzzelli
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D003571:Cytochalasin B / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005340:Fibrinogen / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology; D007700:Kinetics; D016177:Macrophage-1 Antigen / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000097:blood; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D018909:src Homology Domains
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D003571:Cytochalasin B; D014638:Vanadates; D005340:Fibrinogen; D019833:Genistein; D005982:Glutathione Transferase; D011494:Protein Kinases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate