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) |
|---|---|
| Pages (from-to) | 277-288 |
| Number of pages | 12 |
| Journal | EMBO Journal |
| Volume | 10 |
| Issue number | 2 |
| State | Published - 1991 |
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Keywords
- CSF-1
- Growth factor receptor
- Receptor internalization
- Signal transduction
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Cell Biology
- Genetics
Cite this
Role of dimerization and modification of the CSF-1 receptor in its activation and internalization during the CSF-1 response. / Li, Wei; Stanley, E. Richard.
In: EMBO Journal, Vol. 10, No. 2, 1991, p. 277-288.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of dimerization and modification of the CSF-1 receptor in its activation and internalization during the CSF-1 response
AU - Li, Wei
AU - Stanley, E. Richard
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
KW - CSF-1
KW - Growth factor receptor
KW - Receptor internalization
KW - Signal transduction
KW - Tyrosine phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=0025977160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025977160&partnerID=8YFLogxK
M3 - Article
C2 - 1825054
AN - SCOPUS:0025977160
VL - 10
SP - 277
EP - 288
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 2
ER -