Open AccessRibosomal subunit kinase-2 is required for growth factor-stimulated transcription of the c- Fos gene
Author(s) -
Jens C. Brüning,
Jennifer A. Gillette,
Yi Zhao,
Christian Bjorbaeck,
Jörg Kotzka,
Birgit Knebel,
Haluk Avci,
Bettina Hanstein,
Philipp Lingohr,
David E. Moller,
Wilhelm Krone,
C. Ronald Kahn,
Dirk MüllerWieland
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.6.2462
Subject(s) - ribosomal s6 kinase , creb , biology , microbiology and biotechnology , transcription factor , platelet derived growth factor receptor , growth factor , protein kinase a , kinase , phosphorylation , p70 s6 kinase 1 , protein kinase b , receptor , gene , biochemistry
Ribosomal subunit kinases (Rsk) have been implicated in the regulation of transcription by phosphorylating and thereby activating numerous transcription factors, such as c-Fos, cAMP responsive element binding protein (CREB), and nuclear receptors. Here we describe the generation and characterization of immortalized embryonic fibroblast cell lines from mice in which theRsk-2 gene was disrupted by homologous recombinant gene targeting. Rsk-2-deficient (knockout or KO) cell lines have no detectable Rsk-2 protein, whereas Rsk-1 expression is unaltered as compared with cell lines derived from wild-type control mice. KO cells exhibit a major reduction in platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF)-1-stimulated expression of the immediate-early gene c-Fos . This results primarily from a reduced transcriptional activation of the ternary complex factor Elk-1 and reduced activation of the serum response factor. The reduced Elk-1 activation in KO cells occurs despite normal activation of the mitogen-activated protein kinase pathway and normal PDGF- and IGF-1-stimulated Elk-1 phosphorylation. By contrast, PDGF- and IGF-1-stimulated phosphorylation and transcriptional activation of CREB is unaltered in KO cells. Thus Rsk-2 is required for growth factor-stimulated expression of c-Fos and transcriptional activation of Elk-1 and the serum response factor, but not for activation of CREB or the mitogen-activated protein kinase pathway in response to PDGF and IGF-1 stimulation.