Catalog Home Page

Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells

Ingley, E., Schneider, J.R., Payne, C.J., McCarthy, .J., Harder, K.W., Hibbs, M.L. and Klinken, S.P. (2006) Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells. Journal of Biological Chemistry, 281 (42). pp. 31920-31929.

[img]
Preview
PDF - Published Version
Download (672kB) | Preview
Free to read: https://doi.org/10.1074/jbc.M602637200
*No subscription required

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.

Publication Type: Journal Article
Publisher: American Society for Biochemistry and Molecular Biology Inc.
Copyright: © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/39563
Item Control Page Item Control Page

Downloads

Downloads per month over past year