Bradykinin induces tyrosine phosphorylation of epidermal growth factor-receptor and focal adhesion proteins in human keratinocytes.
Bradykinin is an inflammatory mediator which activates signalling pathways in human keratinocytes via a receptor linked to a GTP-binding protein. In the HaCaT human keratinocyte cell line, we observed bradykinin-stimulated tyrosine phosphorylation of several cellular proteins with peak response at 15 min. The focal adhesion proteins paxillin and p125FAK were tyrosine phosphorylated in response to bradykinin but not in response to epidermal growth factor. Interestingly, we identified the epidermal growth factor receptor as a novel target for bradykinin-induced tyrosine phosphorylation. The tyrosine kinase inhibitor genistein and the protein kinase C inhibitors staurosporine and Ro31-7549, all blocked bradykinin-induced tyrosine phosphorylation. Our data suggest that stimulation of the bradykinin receptor leads to activation of a tyrosine kinase activity via a protein-kinase-C-dependent pathway in human keratinocytes.
Coutant
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KD
Department of General Dermatology, SANDOZ Research Institute, Vienna, Austria.
Corvaia
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Ryder
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D000470:Alkaloids / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000302:isolation & purification / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019833:Genistein; D006801:Humans; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D008970:Molecular Weight; D051419:Paxillin; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000502:physiology; D019311:Staurosporine; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D000470:Alkaloids; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007211:Indoles; D007529:Isoflavones; D008301:Maleimides; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D018002:Receptors, Bradykinin; D019000:Phosphotyrosine; D014443:Tyrosine; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D011493:Protein Kinase C; D019311:Staurosporine; D001920:Bradykinin; C064755:Ro 31-7549