Cell Anchorage Permits Efficient Signal Transduction Between Ras and Its Downstream Kinases*
- From the Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599
- ¶ To whom correspondence should be addressed. Tel.: 919-966-4383; Fax: 919-966-5640; E-mail: arjay{at}med.unc.edu
Abstract
Cell anchorage strongly affects the signal transduction cascade initiated by peptide mitogens. For both epidermal growth factor and platelet-derived growth factor, activation of the consensus mitogen-activated protein kinase cascade is impaired when cells are held in suspension as compared with cells anchored to a fibronectin substratum. Upstream events in the signaling cascade, including tyrosine phosphorylation of the mitogen receptor and GTP loading of Ras, are similar in anchored and suspended cells. However, propagation of the signal to Raf and subsequently to the downstream kinases MEK and mitogen-activated protein kinase is markedly attenuated in suspended cells. Thus, there seems to be a distinct anchorage-dependent step between Ras and Raf in the signaling cascade initiated by peptide mitogens. These observations may have important implications for understanding the anchorage dependence of cell growth.
Footnotes
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↵* This work was supported by National Institutes of Health Grants GM26165 and HL45100 (to R. L. J.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- MAP
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mitogen-activated protein
- EGF
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epidermal growth factor
- PDGF
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platelet-derived growth factor
- EGF-R
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EGF receptor
- PDGF-R
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PDGF receptor
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- Received December 17, 1996.
- Revision received January 31, 1997.
- © 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
