Differential phosphorylation of IRS-1 and IRS-2 by insulin and IGF-I receptors

Abstract The specific contribution of insulin and IGF-I receptors to IRS-protein activation remains elusive. We studied the signalling properties of AspB10-insulin, an analog with enhanced affinity for the IGF-I receptor, in comparison to native insulin using primary human skeletal muscle cells. In...

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Bibliographic Details
Published in:Archives of physiology and biochemistry 2006-02, Vol.112 (1), p.37-47
Main Authors: Rakatzi, Irini, Stosik, Magdalene, Gromke, Tanja, Siddle, Kenneth, Eckel, Jürgen
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Differentiation - physiology
Cells, Cultured
Fundamental and applied biological sciences. Psychology
Humans
Hypoglycemic Agents - metabolism
IGF-I receptor
Immunoprecipitation
Insulin - metabolism
Insulin - pharmacology
insulin receptor
Insulin Receptor Substrate Proteins
insulin signalling
Intracellular Signaling Peptides and Proteins
IRS proteins
myoblasts
Myoblasts, Skeletal - cytology
Myoblasts, Skeletal - metabolism
myogenic differentiation
Phosphoproteins - metabolism
Phosphorylation
Receptor, IGF Type 1 - metabolism
Receptor, Insulin - metabolism
Signal Transduction
Striated muscle. Tendons
Tyrosine - metabolism
Vertebrates: osteoarticular system, musculoskeletal system
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Summary:Abstract The specific contribution of insulin and IGF-I receptors to IRS-protein activation remains elusive. We studied the signalling properties of AspB10-insulin, an analog with enhanced affinity for the IGF-I receptor, in comparison to native insulin using primary human skeletal muscle cells. In myoblasts regular insulin and AspB10-insulin were equipotent in stimulating the IRS cascade, whereas this analog induced a significantly higher Shc phosphorylation. Phosphorylation of IRS-1 in response to insulin was inhibited equally by blocking either the insulin or the IGF-I receptor. IRS-1 activation by AspB10-insulin was only inhibited by blocking the IGF-I receptor. IRS-2 phosphorylation induced by both insulin and AspB10-insulin was nearly insensitive to blocking the insulin receptor, being predominantly mediated by the IGF-I receptor. We conclude that in myoblasts IRS-2, but not IRS-1, functions as preferred substrate for the IGF-I receptor. These data suggest a specific role for IRS-2 in growth and differentiation of human skeletal muscle.
ISSN:1381-3455
1744-4160
DOI:10.1080/13813450500500332