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 oncogene products, possibly via activation of the focal adhesion-associated kinase, p125FAK. In the present work, tumor necrosis factor-alpha (TNF) stimulated tyrosine phosphorylation of paxillin in human neutrophils. 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, formylmethionyl-leucyl-phenylalanine and opsonized bacteria. In contrast, p125FAK was constitutively tyrosine phosphorylated in a manner unaffected by adherence and/or TNF. Thus, cytokines and microbial products are among the stimuli that can induce the tyrosine phosphorylation of paxillin, and kinases other than p125FAK may be responsible. This is the first identification of paxillin and p125FAK in human cells and neutrophils, and one of the few identifications of a specific protein that undergoes tyrosine phosphorylation in response to any agonist in neutrophils or in response to TNF in any cell.
Fuortes
M
M
Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York 10021.
Jin
W W
WW
Nathan
C
C
D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism; D002648:Child; D003571:Cytochalasin B / Q000031:analogs & derivatives / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000097:blood / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000097:blood / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D016023:Integrins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; C024794:dihydrocytochalasin B; D003571:Cytochalasin B; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human