Association of JAK2 and STAT5 with erythropoietin receptors. Role of receptor phosphorylation in erythropoietin signal transduction.

The Journal of Biological Chemistry
Stephen T Sawyer, K Penta

Abstract

Cytokine receptors act at least partially by associating with Janus tyrosine protein kinases at the conserved box one motif of the receptor. These receptor-associated kinases then activate STAT transcription factors through phosphorylation. We found that the 78-kDa erythropoietin receptor (EPOR), a highly modified form of the 66-kDa receptor which is abundant in HCD57 cells, was phosphorylated on serine residues without EPO stimulation. Coprecipitation experiments showed the 78-kDa EPOR but not the more abundant 66-kDa EPOR was associated with JAK2, a Janus protein kinase, in both the presence and absence of EPO. Solubilized 78-kDa EPOR bound to purified, genetically engineered JAK2 better than the 62-76-kDa receptor proteins, and additional phosphorylation of tyrosine residues further increased the binding of the 78-kDa EPOR to JAK2-agarose beads. STAT5 DNA binding was activated by 10-100-fold lower concentrations of EPO in HCD57 cells than in primary erythroid cells, and STAT5 associated with the EPOR in an EPO-dependent manner. These data suggest that phosphorylation of either serine or tyrosine residues of the EPOR can enhance the association of the receptor with JAK2, possibly increasing the sensitivity to EPO.

References

Feb 1, 1992·Molecular and Cellular Biology·A Yoshimura, H F Lodish
Dec 15, 1992·European Journal of Biochemistry·M J Koury, M C Bondurant
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J F Bazan
Apr 21, 1989·Cell·A D D'AndreaG G Wong
Jan 1, 1983·Methods in Enzymology·J A CooperT Hunter
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·S Ruff-JamisonS Cohen
Jul 7, 1995·The Journal of Biological Chemistry·C PallardI Dusanter-Fourt
Mar 24, 1995·The Journal of Biological Chemistry·J W TannerA S Shaw
Oct 14, 1994·Biochemical and Biophysical Research Communications·H ZhuangD M Wojchowski
May 1, 1994·Trends in Biochemical Sciences·J N IhleO Silvennoinen
Jun 1, 1994·Molecular and Cellular Biology·S S WatowichH F Lodish
Jan 28, 1994·Cell·T KishimotoS Akira
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S T Sawyer, W D Hankins

❮ Previous
Next ❯

Citations

Jun 21, 2001·Biochemical and Biophysical Research Communications·F AmmarguellatV Goffin
Jan 7, 1998·Cellular Signalling·A SchaeferH Marquardt
Dec 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shahab UddinAmittha Wickrema
Jan 15, 1998·European Journal of Biochemistry·D Sawka-VerhelleE Van Obberghen
Jun 12, 2014·International Journal of Molecular Sciences·Yuanyuan ZhangConstance Tom Noguchi
Feb 23, 1999·Kidney International·C WestenfelderR L Baranowski
Apr 25, 2008·Critical Reviews in Oncology/hematology·Wolfgang JelkmannArthur J Sytkowski
Jul 28, 2009·European Journal of Heart Failure·Katie SmithAnne-Marie L Seymour
May 20, 1999·Current Problems in Pediatrics·S E Juul
Aug 17, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Wojciech KrzyzanskiWing K Cheung
Sep 15, 2000·Clinics in Perinatology·S E Juul
Sep 10, 2014·Journal of Pharmaceutical and Biomedical Analysis·Yushuai YangJunzhi Wang
Jan 26, 2013·International Journal of Molecular Sciences·Maria Letizia TrincavelliClaudia Martini
Jan 29, 2005·The Journal of Biological Chemistry·Virginie Moucadel, Stefan N Constantinescu
Jun 14, 2008·American Journal of Physiology. Cell Physiology·Chhanda Bose, Kodetthoor B Udupa
Apr 26, 2003·Blood·Christopher P ShelburneJohn J Ryan
Jan 24, 1998·The Journal of Biological Chemistry·C LiuC T Noguchi
Mar 14, 1997·The Journal of Biological Chemistry·S M Jacobs-HelberS T Sawyer
Aug 5, 2000·The Journal of Biological Chemistry·Y MiyakawaK Kaushansky
Sep 21, 2000·The Journal of Biological Chemistry·M OgilvieC T Noguchi
May 9, 2000·The Journal of Biological Chemistry·A S BanksM G Myers
Jun 25, 1998·Molecular and Cellular Biology·S M Jacobs-HelberS T Sawyer
Mar 5, 2002·The Journal of Biological Chemistry·Rizwan HaqDwayne L Barber

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.