Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes.

作者: S A McCarthy , M L Samuels , C A Pritchard , J A Abraham , M McMahon

DOI: 10.1101/GAD.9.16.1953

关键词: BiologyGrowth factor receptor inhibitorDifferential displayReceptorSecretionKinaseCell biologySignal transductionEpidermal growth factorDiphtheria toxin

摘要: We have used differential display PCR to search for mRNAs induced by delta Raf-1:ER, an estradiol-dependent form of Raf-1 kinase. Through this approach the gene encoding heparin-binding epidermal growth factor (HB-EGF) was identified as immediate-early transcriptional target oncogenic Raf kinases. Activation Raf-1:ER and a conditional B-Raf, B-RAF:ER, resulted in rapid sustained induction HB-EGF mRNA expression secretion mature from cells. Neutralizing anti-HB-EGF antisera prevented delayed activation c-Jun amino-terminal kinases that is observed cells transformed Raf-1:ER. These results demonstrate distinct signaling pathways can cross talk via polypeptide factors. Furthermore, Ras, which also expression, demonstrated marked increase sensitivity cytotoxic action diphtheria toxin, membrane anchored precursor acts cell-surface receptor.

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