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

AUTOR(ES)

Li, W

RESUMO

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.

Documentos Relacionados

• Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes.
• CSF-1-induced gene expression in macrophages: dissociation from the mitogenic response.
• Activation and inhibition of erythropoietin receptor function: role of receptor dimerization.
• KpnI RFLP for the human CSF-1 gene.
• Nucleotide sequence of a cDNA encoding murine CSF-1 (Macrophage-CSF).