The lyn tyrosine kinase is essential for erythropoietin induced erythroid differentiation and specifically interacts with lckbp-1/hs1 and several novel molecules

E. Ingley, P. A. Tilbrook, J. H. Williams, M. L. Hibbs, S. Tsai, S. P. Klinken

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Erythropoietin (EPO) stimulates the immature erythroid J2E cell line to terminally di.fferentiate, proliferate and maintains their viability in the absence of serum. In contrast, a mutant J2E clone (J2E-NR) fails to mature in response to the hormone which we have shown is due to a very low expression level of the Lyn tyrosine kinase. Co-immunoprecipitation and yeast two-hybrid analysis indicates that Lyn directly associates with the EPO-receptor complex. Using the yeast two hybrid system we have identified LckBP-1/HS1 and several novel molecules as Lyn interactors. LckBP-1/HS1 has been shown to bind to the SH3 domain of Lck and contains four tandem helix-turn-helix motifs, a proline rich region, a proline and glutamine rich segment, and an SH3 domain. The importance of this interaction in EPO-induced signalling through Lyn is currently be!ng investigated. Three novel molecules were also identified in the two-hybrid screen as specifically interacting with Lyn. One of these has an ankyrin repeat most closely related to a K+ channel. Another novel protein bound specifically to a kinase inactive mutant of Lyn where tyrosine 397 had been mutated to phenyalanine. Full-length clones of these novel molecules are currently being isolated and their involvement in erythroid development will be analysed.

Original languageEnglish
JournalThe FASEB Journal
Volume11
Issue number9
Publication statusPublished - 1 Dec 1997

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