Activation of Pyk2 by stress signals and coupling with JNK signaling pathway.
The c-Jun amino-terminal kinase (JNK) is activated by various heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, inflammatory cytokines, and stress signals. Yet, upstream mediators that link extracellular signals with the JNK signaling pathway are currently unknown. The tyrosine kinase Pyk2 was activated by tumor necrosis factor alpha, by ultraviolet irradiation, and by changes in osmolarity. Overexpression of Pyk2 led to activation of JNK, and a dominant-negative mutant of Pyk2 interfered with ultraviolet light- or osmotic shock-induced activation of JNK. Pyk2 represents a cell type-specific, stress-sensitive mediator of the JNK signaling pathway.
Tokiwa
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G
Department of Pharmacology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
Dikic
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I
Lev
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Schlessinger
J
J
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D051418:Focal Adhesion Kinase 2; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009994:Osmolar Concentration; D016716:PC12 Cells; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013012:Sorbitol / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
D014409:Tumor Necrosis Factor-alpha; D013012:Sorbitol; D004533:Egtazic Acid; D000841:Anisomycin; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496054:Ptk2b protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins