PMID- 10025673 OWN - NLM STAT- MEDLINE DCOM- 19990429 LR - 20161124 IS - 0730-2312 (Print) IS - 0730-2312 (Linking) VI - 72 IP - 1 DP - 1999 Jan 1 TI - CSF-1 stimulated multiubiquitination of the CSF-1 receptor and of Cbl follows their tyrosine phosphorylation and association with other signaling proteins. PG - 119-34 AB - Addition of colony stimulating factor-1 (CSF-1) to macrophages stimulates the rapid, transient tyrosine phosphorylation, membrane association and multiubiquitination of Cbl (Wang et al. [1996] J. Biol. Chem. 271:17-20). Kinetic analysis reveals that the tyrosine phosphorylation of Cbl is coincident with its plasma membrane translocation and association with the activated tyrosine phosphorylated CSF-1 R, p85, Grb2, and tyrosine phosphorylated p58Shc and that these events precede the simultaneous multiubiquitination of Cbl and the CSF-1 R. Tyrosine phosphorylation and multiubiquitination of the cell surface CSF-1 R are stoichiometric and the multiubiquitinated CSF-1 R is degraded. Similarly, the membrane associated Cbl is almost stoichiometrically ubiquitinated, but the ubiquitinated Cbl is not degraded, being recovered, deubiquitinated, 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 Sos 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 p58Shc resemble those of Cbl but Sos is not tyrosine phosphorylated, nor multiubiquitinated and the coprecipitation of these proteins, other than Grb2, with Sos is much less. Complexes formed by Sos and Cbl are largely independent and membrane complexes of Cbl with other tyrosine phosphorylated proteins, p85 and Grb2 also contain CSF-1 R. These data raise the possibility that the predicted negative regulatory role of Cbl in macrophages is its enhancement of ligand-induced CSF-1 R internalization/degradation. FAU - Wang, Y AU - Wang Y AD - Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. FAU - Yeung, Y G AU - Yeung YG FAU - Stanley, E R AU - Stanley ER LA - eng GR - CA 26504/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (GRB2 Adaptor Protein) RN - 0 (Grb2 protein, mouse) RN - 0 (Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Ubiquitins) RN - 42HK56048U (Tyrosine) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) RN - EC 6.3.2.- (Cbl protein, mouse) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Animals MH - Cell Line MH - Cell Membrane/metabolism MH - Fluorescent Antibody Technique MH - GRB2 Adaptor Protein MH - Macrophage Colony-Stimulating Factor/*pharmacology MH - Macrophages/*metabolism MH - Mice MH - Molecular Sequence Data MH - Phosphorylation MH - Proteins/metabolism MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-cbl MH - Receptor, Macrophage Colony-Stimulating Factor/drug effects/*metabolism MH - Signal Transduction/physiology MH - Tyrosine/*metabolism MH - *Ubiquitin-Protein Ligases MH - Ubiquitins/*metabolism EDAT- 1999/02/20 03:12 MHDA- 2000/06/20 09:00 CRDT- 1999/02/20 03:12 PHST- 1999/02/20 03:12 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/02/20 03:12 [entrez] AID - 10.1002/(SICI)1097-4644(19990101)72:1<119::AID-JCB13>3.0.CO;2-R [pii] PST - ppublish SO - J Cell Biochem. 1999 Jan 1;72(1):119-34.