Prolonged Activation of ERK2 by Epidermal Growth Factor and Other Growth Factors Requires a Functional Insulin-Like Growth Factor 1 Receptor

• Published in: Endocrinology (Philadelphia) Vol. 140; no. 7; pp. 3163 - 3169
• Main Authors: Swantek, Jennifer L., Baserga, Renato
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-07-1999
• Subjects: Animals; C-Terminus; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell activation; Cell Line; Embryo fibroblasts; Embryos; Enzyme Activation - physiology; Epidermal growth factor; Epidermal Growth Factor - pharmacology; Extracellular signal-regulated kinase; Growth factors; Growth Substances - pharmacology; Humans; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor I receptors; Insulin-like growth factors; Kinases; Mice; Mitogen-Activated Protein Kinase 1; Mutants; Peptide Fragments - metabolism; Platelet-derived growth factor; Platelet-Derived Growth Factor - pharmacology; Protein-serine/threonine kinase; Receptors, Somatomedin - chemistry; Receptors, Somatomedin - metabolism; Receptors, Somatomedin - physiology; Reintroduction; Stimulation
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.140.7.6766

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.