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PMID: 1825054 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of dimerization and modification of the CSF-1 receptor in its activation and internalization during the CSF-1 response.

The EMBO journal ·Vol. 10 ·No. 2 ·1991-02-00 ·Pages 277-88

Li W, Stanley ER

Abstract

We have used kinetic and cross-linking approaches to study CSF-1-induced changes in the structure and function of the CSF-1R. Addition of CSF-1 to cells stimulates or stabilizes non-covalent CSF-1R dimerization resulting in activation of the CSF-1R kinase and the tyrosine phosphorylation of the receptor and certain cytoplasmic proteins. The non-covalent dimers become covalently linked via disulfide bonds and/or are subsequently further modified. These modified forms are selectively internalized. Pre-treatment of cells with the alkylating agent, iodoacetic acid (IAA), selectively inhibits covalent dimerization, modification and internalization but enhances protein tyrosine phosphorylation. It is proposed that ligand-induced non-covalent dimerization activates the CSF-1R kinase, whereas the covalent dimerization and subsequent modification lead to kinase inactivation, phosphotyrosine dephosphorylation and internalization of the receptor--ligand complex.

MeSH Terms
Animals Cell Line Cell Membrane/metabolism Iodoacetates/pharmacology Iodoacetic Acid Kinetics Macromolecular Substances Macrophage Colony-Stimulating Factor/pharmacology Macrophages Models, Biological Molecular Weight Phosphorylation Receptor, Macrophage Colony-Stimulating Factor/drug effects,isolation & purification,metabolism Signal Transduction
Chemicals
Iodoacetates Macromolecular Substances Macrophage Colony-Stimulating Factor Receptor, Macrophage Colony-Stimulating Factor Iodoacetic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Li W
Department of Developmental Biology and Cancer, Albert Einstein College of Medicine, Bronx, NY 10461.
Stanley E R
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-02-00
Pages
277-88
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452644
Subset
IM
Grants
NCI NIH HHS · CA 26504 · United States
NCI NIH HHS · CA 32551 · United States
NCI NIH HHS · P30 CA 13330-16 · United States
External Links
PubMed source PMC Full Text View journal details
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