CSF-1 STIMULATED MULTIUBIQUITINATION OF THE CSF-1 RECEPTOR AND OF CBLFOLLOWS THEIR TYROSINE PHOSPHORYLATION AND ASSOCIATION WITH OTHER SIGNALING PROTEINS

Citation
Y. Wang et al., CSF-1 STIMULATED MULTIUBIQUITINATION OF THE CSF-1 RECEPTOR AND OF CBLFOLLOWS THEIR TYROSINE PHOSPHORYLATION AND ASSOCIATION WITH OTHER SIGNALING PROTEINS, Journal of cellular biochemistry, 72(1), 1999, pp. 119-134
Citations number
60
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
0730-2312
Volume
72
Issue
1
Year of publication
1999
Pages
119 - 134
Database
ISI
SICI code
0730-2312(1999)72:1<119:CSMOTC>2.0.ZU;2-4
Abstract
Addition of colony stimulating factor-1 (CSF-1) to macrophages stimula tes the rapid, transient tyrosine phosphorylation, membrane associatio n and multiubiquitination of Cbl (Wang et at. [1996] J. Biol. Chem. 27 1:17-20). Kinetic analysis reveals that the tyrosine phosphorylation o f Cbl is coincident with its plasma membrane translocation and associa tion with the activated tyrosine phosphorylated CSF-1R, p85, Grb2, and tyrosine phosphorylated p58Shc and that these events precede the simu ltaneous multiubiquitination of Cbl and the CSF-1R. Tyrosine phosphory lation and multiubiquitination of the cell surface CSF-1R are stoichio metric and the multiubiquitinated CSF-1R is degraded. Similarly, the m embrane associated Cbl is almost stoichiometrically ubiquitinated, but the ubiquitinated Cbl is not degraded, being recovered, deubiquitinat ed, in the cytosol 3-10 min after stimulation at 37 degrees C. In the membrane fraction of cells stimulated at 4 degrees C, the association of p58Shc and Grb2 with Cbl is stable, whereas its association with So s and p85 is transient and their dissociation occurs at the time CSF-1 R and Cbl multiubiquitination commence. The membrane translocation and the pattern of association of Sos with the CSF-1R, p85, Grb2, and p58 Shc resemble those of Cbl but Sos is not tyrosine phosphorylated, nor multiubiquitinated and the coprecipitation of these proteins, other th an Grb2, with Sos is much less. Complexes formed by Sos and Cbl are la rgely independent and membrane complexes of Cbl with other tyrosine ph osphorylated proteins, p85 and Grb2 also contain CSF-1R. These data ra ise the possibility that the predicted negative regulatory role of Cbl in macrophages is its enhancement of ligand-induced CSF-1R internaliz ation/ degradation. J. Cell. Biochem. 72.119-134, 1999. (C) 1999 Wiley -Liss, Inc.