Activation of the Protein Kinase ERK5/BMK1 by Receptor Tyrosine Kinases IDENTIFICATION AND CHARACTERIZATION OF A SIGNALING PATHWAY TO THE NUCLEUS

摘要: ERK5 (also known as BMK1), a member of the mitogen-activated protein kinase (MAPK) superfamily, was to be activated strongly by oxidant and osmotic stresses. Here we have found that is epidermal growth factor nerve factor, whose receptors are tyrosine kinases. The activation inhibited expression dominant-negative Ras induced active in PC12 cells, indicating requirement for activation. factor-induced PD98059 U0126 inhibitors, which were previously thought act specifically on classical MAPK MEK1) readily reversed CL100 MKP-3 dual-specificity phosphatases MAPKs shown serve preferred substrates. reporter assays demonstrated serum-induced enhancement transcription from serum response element significantly form MEK5, direct specific activator mediated Ets-domain Sap1a, but not Elk1, stimulated coexpression MEK5. In addition, Sap1a phosphorylated vitro pathway cells. Moreover, c-Fos markedly These results reveal novel signaling nucleus functions downstream receptor kinases induce immediate early genes, parallel with cascade.