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

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131 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalEMBO Journal
Volume10
Issue number2
StatePublished - 1991

Keywords

  • CSF-1
  • Growth factor receptor
  • Receptor internalization
  • Signal transduction
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Molecular Biology
  • General Neuroscience

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