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PMID: 8265614 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 24 ·1993-12-15 ·Pages 11713-7

Lee CH, Li W, Nishimura R, Zhou M, Batzer AG, Myers MG, White MF, Schlessinger J, Skolnik EY

Abstract

Nck, an oncogenic protein composed of one SH2 and three SH3 domains, is a common target for various cell surface receptors. Nck is thought to function as an adaptor protein to couple cell surface receptors to downstream effector molecules that regulate cellular responses induced by receptor activation. In this report, we show that Nck forms a stable complex in vivo with IRS-1 in insulin-stimulated cells. The interaction between IRS-1 and Nck is mediated by the binding of the SH2 domain of Nck to tyrosine-phosphorylated IRS-1. Although Nck associates with IRS-1, Nck phosphorylation is not affected by insulin stimulation. Furthermore, in vitro and in vivo studies show that the SH2 domains of Nck, GRB2, and p85 bind distinct phosphotyrosine residues in IRS-1. After insulin stimulation all three signaling molecules can be found complexed to a single IRS-1 molecule. These findings provide further evidence that, in response to insulin stimulation, IRS-1 acts as an SH2 docking protein that coordinates the regulation of various different signaling pathways activated by the insulin receptor.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Baculoviridae/genetics CHO Cells Cell Line Chromatography, High Pressure Liquid Cricetinae Electrophoresis, Polyacrylamide Gel Insulin/pharmacology Insulin Receptor Substrate Proteins Molecular Sequence Data Moths Oncogene Proteins/isolation & purification,metabolism Peptides/chemical synthesis,isolation & purification Phosphopeptides/chemical synthesis,isolation & purification Phosphoproteins/isolation & purification,metabolism Phosphorylation Protein Binding Receptor, Insulin/biosynthesis,metabolism Signal Transduction Transfection
Chemicals
Adaptor Proteins, Signal Transducing Insulin Insulin Receptor Substrate Proteins Nck protein Oncogene Proteins Peptides Phosphopeptides Phosphoproteins Receptor, Insulin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lee C H
New York University Medical Center, Department of Pharmacology, NY 10016.
Li W
Nishimura R
Zhou M
Batzer A G
Myers M G
White M F
Schlessinger J
Skolnik E Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.24.11713
Published
1993-12-15
Pages
11713-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48054
Subset
IM
Grants
NIDDK NIH HHS · DK438080 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.24.11713 PMC Full Text View journal details
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