Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes
| Autor: | S A McCarthy, Martin McMahon, J A Abraham, Catrin Pritchard, M L Samuels |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Heparin-binding EGF-like growth factor
Proto-Oncogene Proteins c-jun Molecular Sequence Data Retroviridae Proteins Oncogenic Gene Expression Receptors Cell Surface Biology Protein Serine-Threonine Kinases Polymerase Chain Reaction Cell Line Oncogene Proteins v-raf Mice Epidermal growth factor Proto-Oncogene Proteins Genetics Animals Humans Growth factor receptor inhibitor Diphtheria Toxin RNA Messenger Cell Line Transformed DNA Primers Diphtheria toxin Differential display Base Sequence Epidermal Growth Factor Estradiol Kinase Heparin JNK Mitogen-Activated Protein Kinases 3T3 Cells Oncogenes Protein-Tyrosine Kinases Cell biology Proto-Oncogene Proteins c-raf Cell Transformation Neoplastic Genes ras Calcium-Calmodulin-Dependent Protein Kinases Intercellular Signaling Peptides and Proteins Signal transduction Mitogen-Activated Protein Kinases Developmental Biology Heparin-binding EGF-like Growth Factor |
| Zdroj: | Genesdevelopment. 9(16) |
| ISSN: | 0890-9369 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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