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Domains of the insulin-like growth factor I receptor required for the activation of extracellular signal-regulated kinases.

Authors
  • Dews, M
  • Prisco, M
  • Peruzzi, F
  • Romano, G
  • Morrione, A
  • Baserga, R
Type
Published Article
Journal
Endocrinology
Publication Date
Apr 01, 2000
Volume
141
Issue
4
Pages
1289–1300
Identifiers
PMID: 10746631
Source
Medline
License
Unknown

Abstract

The type 1 insulin-like growth factor receptor (IGF-IR) activates the extracellular signal-regulated kinases (ERK1 and -2). The two major substrates of the IGF-IR, insulin receptor substrate-1 (IRS-1) and the Shc proteins, are known to contribute to this activation. We investigated the domains of the IGF-IR required for the activation of the ERK proteins. To facilitate this study, we used a cell line (32D cells) that lacks IRS-1. In the absence of IRS-1, ERK activation is inhibited if the IGF-IR is mutated at two domains: tyrosine Y950 and a serine quartet at 1280-1283. Expression of IRS-1 in 32D cells expressing the double mutant IGF-IR restores ERK activation. The importance of the C-terminus of the IGF-IR in ERK activation (in the absence of IRS-1) is confirmed by the failure of the insulin receptor to give a sustained activation of ERK. In this model system, there is a good, but not exact, correlation between ERK activation and cell survival after withdrawal of growth factors.

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