Journal article
Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells
Journal of Biological Chemistry, Vol.281(42), pp.31920-31929
2006
Abstract
We have shown previously that the Src family kinase Lyn is involved in differentiation signals emanating from activated erythropoietin (Epo) receptors. The importance of Lyn to red cell maturation has been highlighted by Lyn -/- mice developing anemia. Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr 314, which recruited Csk/Ctk to suppress Lyn kinase activity. Intriguingly, phosphorylated Tyr314 also bound suppressor of cytokine signaling 1 (SOCS1), another well characterized negative regulator of cell signaling, resulting in elevated ubiquitination, and degradation of Lyn. In Epo-responsive primary cells and cell lines, Lyn rapidly phosphorylated Cbp, suppressing Lyn kinase activity via Csk/Ctk within minutes of Epo stimulation; hours later, SOCS1 bound to Cbp and was involved in the ubiquitination and turnover of Lyn protein. Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn.
Details
- Title
- Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells
- Authors/Creators
- E. Ingley (Author/Creator) - The University of Western AustraliaJ.R. Schneider (Author/Creator) - The University of Western AustraliaC.J. Payne (Author/Creator) - The University of Western Australia.J. McCarthy (Author/Creator)K.W. Harder (Author/Creator) - The Royal Melbourne HospitalM.L. Hibbs (Author/Creator) - The Royal Melbourne HospitalS.P. Klinken (Author/Creator) - The University of Western Australia
- Publication Details
- Journal of Biological Chemistry, Vol.281(42), pp.31920-31929
- Publisher
- American Society for Biochemistry and Molecular Biology Inc.
- Identifiers
- 991005541296907891
- Copyright
- © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.184 Physiology & Metals
- 1.184.1030 Erythropoietin Therapy
- Web Of Science research areas
- Biochemistry & Molecular Biology
- ESI research areas
- Biology & Biochemistry