Homodimerization restores biological activity to an inactive erythropoietin mutant.

The Journal of Biological Chemistry
H QiuH F Bunn

Abstract

Erythropoietin (Epo) is believed to transduce a signal by bringing two Epo receptors into close proximity, enabling cross-phosphorylation. We compared monomeric Epos with homodimers in which two Epo monomers are linked by polyglycine. Monomeric Epo mutant R103A is unable to support Epo-dependent cell growth or trigger Janus kinase 2 and STAT5 activation, even at concentrations greater than 7,000 times that sufficient for wild-type Epo activity. In contrast, R103A homodimer induces proliferation and transduces signal at concentrations similar to that of wild-type Epo monomer and homodimer. These experiments show that two discrete domains on Epo are required for receptor binding and activation. Our results also suggest that the EpoR can be dimerized by different forms and sizes of molecules, as long as two recognition motifs are provided in the same molecule. Design of other dimeric molecules may enhance our understanding of cytokine specificity and signal transduction.

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S S WatowichH F Lodish
Oct 1, 1990·Immunology Today·J F Bazan
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M A GoldbergH F Bunn
Jan 1, 1993·Annual Review of Biophysics and Biomolecular Structure·J A Wells, A M de Vos
Apr 1, 1994·Current Opinion in Cell Biology·J A Wells
Jun 1, 1994·Molecular and Cellular Biology·S S WatowichH F Lodish
Mar 22, 1996·The Journal of Biological Chemistry·P A HardingJ J Kopchick
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·D J MatthewsL B Giebel
Oct 4, 1996·The Journal of Biological Chemistry·S ElliottG Elliott
Jan 1, 1995·Cold Spring Harbor Symposia on Quantitative Biology·H F LodishH Wu

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Citations

Dec 23, 1999·Current Opinion in Structural Biology·I A Wilson, L K Jolliffe
Oct 24, 1998·Bioorganic & Medicinal Chemistry·D L BogerC M Andersson
Apr 20, 2001·Bioorganic & Medicinal Chemistry·D L Boger, J Goldberg
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·S K Ruscetti
Nov 10, 1998·Nature Structural Biology·M D Ballinger, J A Wells
Jun 3, 2000·The EMBO Journal·J Bravo, J K Heath
May 6, 2004·Science's STKE : Signal Transduction Knowledge Environment·Robert M Stroud, James A Wells
Jan 31, 2012·Reproductive Biology and Endocrinology : RB&E·Seong-Jo YunKwan-Sik Min
Oct 31, 2000·Bioscience, Biotechnology, and Biochemistry·R SasakiM Nagao
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·A L BarnettJ M Cunningham
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·H ZhuH F Bunn
Feb 26, 2008·Experimental Hematology·Olivier NegreEmmanuel Payen
Nov 4, 2006·Analytical Biochemistry·Natasa DebeljakArthur J Sytkowski
Nov 30, 2005·Biochemical and Biophysical Research Communications·Dong Eok LeeOok Joon Yoo
Oct 25, 2003·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·A S RamosS L Dalmora
Oct 11, 2012·Critical Reviews in Biochemistry and Molecular Biology·Mariya Atanasova, Adrian Whitty
Oct 13, 2006·Blood·H Franklin Bunn
Jan 14, 2003·Experimental Biology and Medicine·James W Fisher

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