Abstract
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. Here, 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 alpha and fMLP stimulation in an adhesion-dependent manner. Tyrosine phosphorylation of Pyk2 was attenuated by beta2 integrin blocking with specific antibodies. The tyrosine phosphorylation of Pyk2 was downstream of protein kinases Lyn, Syk and protein kinase C and cytoskeletal organization. The activation of Pyk2 may play a role in adhesion/cytoskeleton-associated neutrophils function.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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CD18 Antigens / metabolism*
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Cell Adhesion
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Cell Fractionation
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Cytoskeleton / metabolism
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Enzyme Activation
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Enzyme Precursors / metabolism
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Fibronectins / metabolism*
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Focal Adhesion Kinase 2
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Humans
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Intracellular Signaling Peptides and Proteins
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N-Formylmethionine Leucyl-Phenylalanine / metabolism*
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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Neutrophils / drug effects
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Neutrophils / metabolism*
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Neutrophils / physiology
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Phosphorylation
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Protein Kinase C / metabolism
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Protein-Tyrosine Kinases / metabolism*
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Syk Kinase
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Tumor Necrosis Factor-alpha / metabolism*
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Tumor Necrosis Factor-alpha / pharmacology
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src-Family Kinases / metabolism
Substances
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CD18 Antigens
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Enzyme Precursors
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Fibronectins
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Intracellular Signaling Peptides and Proteins
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Tumor Necrosis Factor-alpha
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N-Formylmethionine Leucyl-Phenylalanine
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 2
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SYK protein, human
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Syk Kinase
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lyn protein-tyrosine kinase
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src-Family Kinases
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Protein Kinase C