Abstract
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.
References
80
Referenced
152
10.1126/science.1659742
10.1006/bbrc.1993.1020
{'key': '2021111418243657000_9.16.1953.3', 'first-page': '2140', 'article-title': 'Complexity of the early genetic response to growth factors in fibroblasts.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Complexity of the early genetic response to growth factors in fibroblasts. (1988)- Ausubel, F.M., R. Brent, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl. 1987. Current protocols in molecular biology. John Wiley and Sons, New York.
10.1016/S0021-9258(17)31718-0
/ J. Biol. Chem. / Auto- and cross-induction within the mammalian epidermal growth factor-related peptide family. (1994)10.1016/0092-8674(94)90023-X
10.1073/pnas.91.8.2890
{'key': '2021111418243657000_9.16.1953.8', 'first-page': '4682', 'article-title': 'Ras oncogenes in human cancer: A review.', 'volume': '49', 'year': '1989', 'journal-title': 'Cancer Res.'}
/ Cancer Res. / Ras oncogenes in human cancer: A review. (1989){'key': '2021111418243657000_9.16.1953.9', 'first-page': '3379', 'article-title': 'Constitutively active mutants of MAP kinase kinase (MEK1) induce growth factor relaxation and oncogenicity when expressed in fibroblasts.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'}
/ Oncogene / Constitutively active mutants of MAP kinase kinase (MEK1) induce growth factor relaxation and oncogenicity when expressed in fibroblasts. (1994)10.1038/370386a0
{'key': '2021111418243657000_9.16.1953.11', 'first-page': '2349', 'article-title': 'Inhibition of growth of Erlich tumours in Swiss mice by diphtheria toxin.', 'volume': '33', 'year': '1973', 'journal-title': 'Cancer Res.'}
/ Cancer Res. / Inhibition of growth of Erlich tumours in Swiss mice by diphtheria toxin. (1973)10.1210/mend-2-12-1202
{'key': '2021111418243657000_9.16.1953.13', 'first-page': '407', 'article-title': 'Transforming growth factor-alpha expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras protooncogene but not by the c-neu protooncogene, and overexpression of the transforming growth factor-alpha complementary DNA leads to transformation.', 'volume': '1', 'year': '1990', 'journal-title': 'Cell Growth Differ.'}
/ Cell Growth Differ. / Transforming growth factor-alpha expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras protooncogene but not by the c-neu protooncogene, and overexpression of the transforming growth factor-alpha complementary DNA leads to transformation. (1990)10.1016/0092-8674(94)90133-3
10.1073/pnas.75.8.4001
10.1016/0092-8674(94)90380-8
10.1016/0959-437X(94)90092-2
10.1016/S0021-9258(17)46848-7
/ J. Biol. Chem. / Heparin-binding epidermal growth factor-like growth factor expression in cultured fetal human vascular smooth muscle cells. Induction of mRNA levels and secretion of active mitogen. (1993)10.1038/365781a0
{'key': '2021111418243657000_9.16.1953.20', 'first-page': '1017', 'article-title': 'Role of transforming growth factor alpha in the transformation of ras-transfected rat intestinal epithelial cells.', 'volume': '8', 'year': '1993', 'journal-title': 'Oncogene'}
/ Oncogene / Role of transforming growth factor alpha in the transformation of ras-transfected rat intestinal epithelial cells. (1993)10.1073/pnas.89.16.7355
10.1126/science.7824938
10.1016/S0021-9258(18)42397-6
/ J. Biol. Chem. / MAP kinase is constitutively activated in gip2 and src transformed rat 1a fibroblasts. (1992)10.1084/jem.182.1.147
10.1016/S0021-9258(17)32127-0
/ J. Biol. Chem. / Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes. (1994){'key': '2021111418243657000_9.16.1953.26', 'first-page': '1265', 'article-title': 'Transformation of NIH3T3 fibroblasts by an expression vector for the human Epidermal Growth Factor precursor.', 'volume': '5', 'year': '1990', 'journal-title': 'Oncogene'}
/ Oncogene / Transformation of NIH3T3 fibroblasts by an expression vector for the human Epidermal Growth Factor precursor. (1990)10.1146/annurev.bi.60.070191.001433
10.1016/0092-8674(95)90402-6
10.1101/gad.7.11.2135
10.1126/science.1840698
10.1016/S0021-9258(18)42682-8
/ J. Biol. Chem. / Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. (1992)10.1083/jcb.122.4.933
10.1016/0092-8674(95)90403-4
10.1016/0092-8674(93)90238-L
10.1016/0092-8674(92)90162-6
10.1073/pnas.71.7.2707
10.1016/0042-6822(75)90029-X
10.1016/0016-5085(94)90823-0
/ Gastroenterology / Expression of heparin-binding epidermal growth factor in human hepatocellular carcinoma. (1994)10.1006/bbrc.1994.1004
10.1002/j.1460-2075.1994.tb06516.x
/ EMBO J. / Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. (1994)10.1016/0955-0674(94)90035-3
10.1006/bbrc.1994.2131
10.1038/369156a0
10.1126/science.8073291
10.1126/science.8385802
10.1126/science.1354393
10.1093/nar/21.14.3269
10.1016/0092-8674(93)90237-K
10.1016/0959-437X(94)90095-7
10.1016/0092-8674(95)90401-8
10.1016/S0021-9258(19)36656-6
/ J. Biol. Chem. / Responses of pertussis toxin-treated microvascular endothelial cells to transforming growth factor beta. (1992)10.1128/mr.48.3.199-221.1984
/ Microbiol. Rev. / Bacterial toxins: Cellular mechanisms of action. (1984)10.1126/science.7992057
{'key': '2021111418243657000_9.16.1953.54', 'first-page': '6683', 'article-title': 'c-jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen activated protein kinases.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / c-jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen activated protein kinases. (1994)10.1006/bbrc.1993.2469
{'key': '2021111418243657000_9.16.1953.56', 'first-page': '377', 'article-title': 'The Raf-1 kinase as a transducer of mitogenic signals.', 'volume': '2', 'year': '1990', 'journal-title': 'Cancer Cells'}
/ Cancer Cells / The Raf-1 kinase as a transducer of mitogenic signals. (1990)10.1016/0092-8674(92)90623-K
10.1073/pnas.89.6.2170
10.1073/pnas.91.3.1069
10.1016/S0021-9258(18)41617-1
/ J. Biol. Chem. / Glucocorticoid inhibits thrombin-induced expression of platelet-derived growth factor A-chain and heparin-binding epidermal growth factor-like growth factor in human aortic smooth muscle cells. (1993)10.1016/0968-0004(93)90019-J
10.1016/S0021-9258(19)41496-8
/ J. Biol. Chem. / High resolution two-dimensional electrophoresis of proteins. (1975)10.1016/0092-8674(94)90580-0
10.1146/annurev.bi.46.070177.000441
10.1016/S0021-9258(18)47123-2
/ J. Biol. Chem. / Regulation of heparin-binding epidermal growth factor-like growth factor mRNA levels by hypertrophic stimuli in neonatal and adult rat cardiac myocytes. (1994)10.1006/bbrc.1994.2500
{'key': '2021111418243657000_9.16.1953.67', 'first-page': '495', 'article-title': 'Role of Raf-1 serine/threonine protein kinase in growth factor signal transduction.', 'volume': '6', 'year': '1991', 'journal-title': 'Oncogene'}
/ Oncogene / Role of Raf-1 serine/threonine protein kinase in growth factor signal transduction. (1991)10.1016/0092-8674(95)90006-3
10.1074/jbc.270.20.11757
{'key': '2021111418243657000_9.16.1953.70', 'first-page': '6241', 'article-title': 'Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase. (1993){'key': '2021111418243657000_9.16.1953.71', 'first-page': '7855', 'article-title': 'Inhibition of PDGF and EGF-mediated mitogenesis and signaling in 3T3 cells expressing ΔRaf-1:ER, an estradiol-regulated form of Raf-1.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Inhibition of PDGF and EGF-mediated mitogenesis and signaling in 3T3 cells expressing ΔRaf-1:ER, an estradiol-regulated form of Raf-1. (1994)10.1038/372794a0
10.1126/science.3492043
10.1098/rstb.1993.0066
10.1016/0092-8674(94)90056-6
10.1006/bbrc.1994.2028
10.1016/0042-6822(79)90183-1
10.1016/S0021-9258(18)35847-2
/ J. Biol. Chem. / Induction of heparin-binding epidermal growth factor-like growth factor mRNA by phorbol ester and angiotensin II in rat aortic smooth muscle cells. (1992)10.1038/372798a0
10.1016/S0021-9258(19)50112-0
/ J. Biol. Chem. / Tumor necrosis factor increases transcription of the heparin-binding epidermal growth factor-like growth factor gene in vascular endothelial cells. (1992)
Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 9:39 p.m.) |
Indexed | 3 months ago (May 25, 2025, 9:42 a.m.) |
Issued | 30 years ago (Aug. 15, 1995) |
Published | 30 years ago (Aug. 15, 1995) |
Published Online | 30 years ago (Aug. 15, 1995) |
Published Print | 30 years ago (Aug. 15, 1995) |
@article{McCarthy_1995, title={Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes.}, volume={9}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.9.16.1953}, DOI={10.1101/gad.9.16.1953}, number={16}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={McCarthy, S A and Samuels, M L and Pritchard, C A and Abraham, J A and McMahon, M}, year={1995}, month=aug, pages={1953–1964} }