This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Funakoshi-Tago, M.
Right arrow Articles by Ihle, J. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Funakoshi-Tago, M.
Right arrow Articles by Ihle, J. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2008, p. 1792-1801, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01447-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Jak2 FERM Domain Interaction with the Erythropoietin Receptor Regulates Jak2 Kinase Activity{triangledown}

Megumi Funakoshi-Tago, Stéphane Pelletier, Hiroshi Moritake, Evan Parganas, and James N. Ihle*

Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Received 10 August 2007/ Returned for modification 28 September 2007/ Accepted 11 December 2007

Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled. In a screen to identify phosphorylation events regulating Jak2 activity in EpoR signaling, we identified a mutant (Jak2-Y613E) which has the property of being constitutively activated, as well as an inactivating mutation (Y766E). Although no evidence was obtained to indicate that either site is phosphorylated in signaling, the consequences of the Y613E mutation are similar to those observed with recently described activating mutations in Jak2 (Jak2-V617F and Jak2-L611S). However, unlike the V617F or L611S mutant, the Y613E mutant requires the presence of the receptor but not Epo stimulation for activation and downstream signaling. The properties of the Jak2-Y613E mutant suggest that under normal conditions, Jak2 that is not associated with a receptor is locked into an inactive state and receptor binding through the FERM domain relieves steric constraints, allowing the potential to be activated with receptor engagement.

* Corresponding author. Mailing address: Department of Biochemistry, D4013, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105. Phone: (901) 495-3422. Fax: (901) 525-8025. E-mail: james.ihle{at}stjude.org

{triangledown} Published ahead of print on 26 December 2007.

Molecular and Cellular Biology, March 2008, p. 1792-1801, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01447-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Robertson, S. A., Koleva, R. I., Argetsinger, L. S., Carter-Su, C., Marto, J. A., Feener, E. P., Myers, M. G. Jr. (2009). Regulation of Jak2 Function by Phosphorylation of Tyr317 and Tyr637 during Cytokine Signaling. Mol. Cell. Biol. 29: 3367-3378 [Abstract] [Full Text]  
  • Mullighan, C. G., Zhang, J., Harvey, R. C., Collins-Underwood, J. R., Schulman, B. A., Phillips, L. A., Tasian, S. K., Loh, M. L., Su, X., Liu, W., Devidas, M., Atlas, S. R., Chen, I-M., Clifford, R. J., Gerhard, D. S., Carroll, W. L., Reaman, G. H., Smith, M., Downing, J. R., Hunger, S. P., Willman, C. L. (2009). JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. USA 106: 9414-9418 [Abstract] [Full Text]  
  • Gery, S., Cao, Q., Gueller, S., Xing, H., Tefferi, A., Koeffler, H. P. (2009). Lnk inhibits myeloproliferative disorder-associated JAK2 mutant, JAK2V617F. J. Leukoc. Biol. 85: 957-965 [Abstract] [Full Text]  
  • Funakoshi-Tago, M., Tago, K., Sumi, K., Abe, M., Aizu-Yokota, E., Oshio, T., Sonoda, Y., Kasahara, T. (2009). The Acute Lymphoblastic Leukemia-associated JAK2 L611S Mutant Induces Tumorigenesis in Nude Mice. J. Biol. Chem. 284: 12680-12690 [Abstract] [Full Text]  
  • Plo, I., Nakatake, M., Malivert, L., de Villartay, J.-P., Giraudier, S., Villeval, J.-L., Wiesmuller, L., Vainchenker, W. (2008). JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders. Blood 112: 1402-1412 [Abstract] [Full Text]  
  • Gakovic, M., Ragimbeau, J., Francois, V., Constantinescu, S. N., Pellegrini, S. (2008). The Stat3-activating Tyk2 V678F Mutant Does Not Up-regulate Signaling through the Type I Interferon Receptor but Confers Ligand Hypersensitivity to a Homodimeric Receptor. J. Biol. Chem. 283: 18522-18529 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»