Effect of Mutations at Serines 1280
1283 on the Mitogenic and Transforming Activities of the Insulin-like Growth Factor I Receptor (*)
- § To whom correspondence should be addressed. Tel.: 215-503-4507; Fax: 215-923-0249.
Abstract
The insulin-like growth factor I receptor (IGF-IR) controls the extent of cell proliferation in a variety of cell types by
at least 3 different ways: it is mitogenic, it causes transformation, and it protects cells from apoptosis. Previous reports
indicated that certain domains in the C terminus of the IGF-IR transmitted a transforming signal that is additional to and
separate from the mitogenic signal. We have now mutated the four serine residues at 1280-1283 of the IGF-IR, and transfected
the mutant receptor into R
cells. Cells expressing the mutant receptor are fully responsive to IGF-I-mediated mitogenesis, but are not transformed (no
colony formation in soft agar). Several downstream signal transducers are not affected by the mutation, again suggesting a
separate pathway for transformation. The mutant receptor can act as a dominant negative for growth, but cannot induce apoptosis
in cells with endogenous wild-type receptors.
Footnotes
-
↵* This work has been supported by funds from the National Institutes of Health, National Institute on Aging Grant AG00378. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵(
) The abbreviations used are:
- IGF-IR
-
insulin-like growth factor I receptor
- IGF-I or II
-
insulin-like growth factor I or II
- IR
-
insulin receptor
- SFM
-
serum-free medium
- PCR
-
polymerase chain reaction
- PI-3
-
phosphoinositide 3
- MAP
-
mitogen-activated protein
- PCR
-
polymerase chain reaction
- DMEM
-
Dulbecco's modified Eagle's medium
- PAGE
-
polyacrylamide gel electrophoresis
- IRS-1
-
insulin receptor substrate-1.
-
↵(
) J.-L. Burgaud and R. Baserga, submitted for publication.
-
↵(
) C. D'Ambrosio, A. Ferber, M. Resnicoff, and R. Baserga, unpublished data.
-
- Received October 31, 1995.
- Revision received January 5, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
