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 language | English (US) |
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Pages (from-to) | 277-288 |
Number of pages | 12 |
Journal | EMBO Journal |
Volume | 10 |
Issue number | 2 |
State | Published - 1991 |
Keywords
- CSF-1
- Growth factor receptor
- Receptor internalization
- Signal transduction
- Tyrosine phosphorylation
ASJC Scopus subject areas
- General Immunology and Microbiology
- General Biochemistry, Genetics and Molecular Biology
- Molecular Biology
- General Neuroscience