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Exp Clin Endocrinol Diabetes 2005; 113(2): 94-101
DOI: 10.1055/s-2004-830554
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Reduced Phosphorylation of Transcription Factor Elk-1 in Cultured Fibroblasts of a Patient with Premature Aging Syndrome and Insulin Resistance

B. Knebel1 , H. Avci1 , C. Bullmann1 , J. Kotzka1 , D. Müller-Wieland1
  • 1Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine University Düsseldorf, Member of the Leibniz Society, Düsseldorf, Germany
Further Information

Publication History

Received: February 9, 2004 First decision: May 6, 2004

Accepted: September 9, 2004

Publication Date:
17 March 2005 (online)

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Abstract

The effect of insulin and growth factor mediated signaling to gene regulation was investigated in cultured fibroblasts of a patient with a premature aging syndrome (metageria) and severe insulin resistance. Insulin receptor structure and function as well as major pathways activated by insulin, i.e. phosphatidyl inositol‐3 kinase (PI-3 K) cascade or mitogen-activated protein kinase (MAPK) cascades, were functional. Inducibility of the proto-oncogene cfos, a representative endpoint of signaling pathways related to gene expression, by growth factors or insulin was reduced in patient cells. This reduced induction persisted in cfos promoter reporter gene studies indicating that the post receptor defect is localized proximal to the cfos promoter itself. Abundances of the transcription factors Elk-1 and SRF being major players in coupling of MAPKs to cfos promoter activation were not altered. However, basal and inducible phosphorylation of Elk-1 was impaired. In addition, basal and stimulated transcriptional activity mediated by Elk-1 was almost abolished in patient cells. Therefore these results identify a post receptor defect in cFos induction, which appears to be related to a functional alteration of Elk-1. A possible relation of this signal transduction defect to the specific premature aging syndrome remains to be elucidated.

Key words

Insulin resistance - signal transduction - cFos promoter - transcription factor Elk-1 - premature aging

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MD Dirk Müller-Wieland

Institut für Klinische Biochemie und Pathobiochemie
Deutsches Diabetes Zentrum

Auf'm Hennekamp 65

40225 Düsseldorf

Germany

Phone: + 492113382240

Fax: + 49 21 13 38 24 30

Email: mueller-wieland@ddfi.uni-duesseldorf.de

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