BRADYKININ INDUCES TYROSINE PHOSPHORYLATION OF EPIDERMAL GROWTH FACTOR-RECEPTOR AND FOCAL ADHESION PROTEINS IN HUMAN KERATINOCYTES

Bradykinin is an inflammatory mediator which activates signalling path ways in human keratinocytes via a receptor linked to a GTP-binding pro tein. In the HaCaT human keratinocyte cell line, we observed bradykini n-stimulated tyrosine phosphorylation of several cellular proteins wit h peak response at 15 min. The focal adhesion proteins paxillin and p1 25(FAK) 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 genist ein and the protein kinase C inhibitors staurosporine and Ro31-7549, a ll blocked bradykinin-induced tyrosine phosphorylation. Our data sugge st that stimulation of the bradykinin receptor leads to activation of a tyrosine kinase activity via a protein-kinase-C-dependent pathway in human keratinocytes. (C) 1995 Academic Press, Inc.