| First Author | McCarthy SA | Year | 1995 |
| Journal | Genes Dev | Volume | 9 |
| Issue | 16 | Pages | 1953-64 |
| PubMed ID | 7649477 | Mgi Jnum | J:28434 |
| Mgi Id | MGI:76051 | Doi | 10.1101/gad.9.16.1953 |
| Citation | McCarthy SA, et al. (1995) Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. Genes Dev 9(16):1953-64 |
| abstractText | 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 an immediate-early transcriptional target of oncogenic Raf kinases. Activation of delta Raf-1:ER and a conditional oncogenic form of B-Raf, delta B-RAF:ER, resulted in rapid and sustained induction of HB-EGF mRNA expression and secretion of mature HB-EGF from cells. Neutralizing anti-HB-EGF antisera prevented the delayed activation of the c-Jun amino-terminal kinases that is observed in cells transformed by delta Raf-1:ER. These results demonstrate that distinct signaling pathways can cross talk via the secretion of polypeptide growth factors. Furthermore, cells transformed by oncogenic Ras, which also induced HB-EGF expression, demonstrated a marked increase in sensitivity to the cytotoxic action of diphtheria toxin, for which the membrane anchored HB-EGF precursor acts as a cell-surface receptor. |
