title: p38 MAP kinase enhances EGF-induced apoptosis in A431 carcinoma cells by promoting tyrosine phosphorylation of STAT1.
abstract: While epidermal growth factor (EGF) is a well known mitogen, high doses of EGF result in a paradoxical apoptotic response in the cells that overexpress EGF receptor such as A431 epidermoid carcinoma cells. EGF-induced apoptosis in A431 cells is dependent upon activation of transcription factor STAT1. In this study, we demonstrate that p38 MAP kinase is another important mediator of EGF-dependent pro-apoptotic response in A431 cells. By utilizing p38 MAP kinase inhibitors, SB203580 and BIRB0796, we significantly reduced the integral growth-inhibiting as well as pro-apoptotic effects of EGF. Moreover, we observed that inhibition of p38 MAP kinase markedly decreased phosphorylation of tyrosine 701 in STAT1, while neither EGF-induced accumulation nor serine phosphorylation of STAT1 was decreased. We propose that p38 MAP kinase mediates STAT1 tyrosine phosphorylation, thereby enforcing EGF-induced apoptosis.
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology RAS, St. Petersburg, Russian Federation.
authors.forename: Polina Y
authors.initials: PY
authors.lastname: Kozyulina
authors.forename: Larisa S
authors.initials: LS
authors.lastname: Okorokova
authors.forename: Nikolay N
authors.initials: NN
authors.lastname: Nikolsky
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Grudinkin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014443:Tyrosine; D004815:Epidermal Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases