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Stress kinase p38 mediates EGFR transactivation by hyperosmolar concentrations of sorbitol
Author(s) -
Cheng Hao,
Kartenbeck Jürgen,
Kabsch Kirsten,
Mao Xiahong,
Marqués Margarita,
Alonso Angel
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10134
Subject(s) - microbiology and biotechnology , transactivation , epidermal growth factor receptor , dephosphorylation , kinase , chemistry , p38 mitogen activated protein kinases , gtpase , phosphorylation , cdc42 , receptor , cancer research , protein kinase a , biology , biochemistry , phosphatase , transcription factor , gene
Activation of the epidermal growth factor receptor (EGFR) has been shown to occur by ligand‐dependent and ligand‐independent mechanisms. Different molecular mechanisms have been found to be responsible for ligand‐independent receptor transactivation. Here, we show that hyperosmolar concentrations of sorbitol activate the EGFR in human keratinocytes. Experiments using specific inhibitors of EGFR phosphorylation show that the increased amount of activated receptors is the result of a decreased rate of dephosphorylation. Furthermore, sorbitol treatment results in a strong activation of stress kinase p38. Treatment of the cells with SB203580, a known inhibitor of p38 α and β kinases, results in impairment of receptor activation, indicating that the stress kinase is involved in receptor activation modulation. This is further reinforced by experiments showing that addition of Toxin B, known to be an inhibitor of the small Rho GTPases rac1, cdc42, and Rho A/B, to the cells results in a strong induction of EGFR activation. Our results point, therefore, to a mechanism by which osmotic shock activates EGFR through the small Rho GTPases‐p38 stress kinase pathway. © 2002 Wiley‐Liss, Inc.