MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 Mazurkiewicz-Munoz, A. M.
Right arrow Articles by Carter-Su, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mazurkiewicz-Munoz, A. M.
Right arrow Articles by Carter-Su, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2006, p. 4052-4062, Vol. 26, No. 11
0270-7306/06/$08.00+0     doi:10.1128/MCB.01591-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Phosphorylation of JAK2 at Serine 523: a Negative Regulator of JAK2 That Is Stimulated by Growth Hormone and Epidermal Growth Factor

Anna M. Mazurkiewicz-Munoz,1,{dagger} Lawrence S. Argetsinger,2,{dagger} Jean-Louis K. Kouadio,2 Allan Stensballe,3 Ole N. Jensen,3 Joel M. Cline,2 and Christin Carter-Su2*

Graduate Program in Cellular and Molecular Biology,1 Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0622,2 Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark3

Received 17 August 2005/ Returned for modification 20 September 2005/ Accepted 8 March 2006

The tyrosine kinase JAK2 is a key signaling protein for at least 20 receptors in the cytokine/hematopoietin receptor superfamily and is a component of signaling for multiple receptor tyrosine kinases and several G-protein-coupled receptors. In this study, phosphopeptide affinity enrichment and mass spectrometry identified serine 523 (Ser523) in JAK2 as a site of phosphorylation. A phosphoserine 523 antibody revealed that Ser523 is rapidly but transiently phosphorylated in response to growth hormone (GH). MEK1 inhibitor UO126 suppresses GH-dependent phosphorylation of Ser523, suggesting that extracellular signal-regulated kinases (ERKs) 1 and/or 2 or another kinase downstream of MEK1 phosphorylate Ser523 in response to GH. Other ERK activators, phorbol 12-myristate 13-acetate and epidermal growth factor, also stimulate phosphorylation of Ser523. When Ser523 in JAK2 was mutated, JAK2 kinase activity as well as GH-dependent tyrosyl phosphorylation of JAK2 and Stat5 was enhanced, suggesting that phosphorylation of Ser523 inhibits JAK2 kinase activity. We hypothesize that phosphorylation of Ser523 in JAK2 by ERKs 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner to dampen activation of JAK2 in response to GH and provides a mechanism by which prior exposure to environmental factors that regulate Ser523 phosphorylation might modulate the cell's response to GH.

* Corresponding author. Mailing address: Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109-0622. Phone: (734) 763-2561. Fax: (734) 647-9523. E-mail: cartersu{at}umich.edu.

{dagger} These two authors contributed equally to this work.

Molecular and Cellular Biology, June 2006, p. 4052-4062, Vol. 26, No. 11
0270-7306/06/$08.00+0     doi:10.1128/MCB.01591-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2006 by the American Society for Microbiology. All rights reserved.