Prolonged activation of ERK2 by epidermal growth factor and other growth factors requires a functional insulin-like growth factor 1 receptor.

Abstract:

:We have investigated the activation of ERK2, a serine/threonine kinase necessary for transmission of mitogenic signals, in cells derived from mouse embryos homozygous for a null mutation of the insulin-like growth factor (IGF)-1R gene (R- cells) and from wild-type littermates (W cells), respectively. Stimulation of quiescent W cells with IGF-1, epidermal growth factor (EGF), or with a combination growth factors induced both a maximal transient and a prolonged activation of ERK2, whereas platelet-derived growth factor or a combination of platelet-derived growth factor and EGF resulted only in transient activation of ERK2. In contrast, stimulation of R cells with IGF-1, EGF, or combinations of growth factors resulted in a transient and submaximal activation of ERK2. Reintroduction of a wild-type human IGF-1R or of a C-terminus IGF-1R mutant, but not of a juxtamembrane mutant IGF-1R, into R- cells was able to restore ERK2 activation to wild-type levels. Thus, prolonged ERK2 activation in mouse embryo fibroblasts stimulated with purified growth factors is largely dependent on a signal generated by the IGF-1R.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Swantek JL,Baserga R

doi

10.1210/endo.140.7.6766

subject

Has Abstract

pub_date

1999-07-01 00:00:00

pages

3163-9

issue

7

eissn

0013-7227

issn

1945-7170

journal_volume

140

pub_type

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