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 Migone, T.-S.
Right arrow Articles by Leonard, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Migone, T.-S.
Right arrow Articles by Leonard, W. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 1998, p. 6416-6422, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Cooperation of the Interleukin-2 Receptor beta  Chain and Jak1 in Phosphatidylinositol 3-Kinase Recruitment and Phosphorylation

Thi-Sau Migone,1,dagger Scott Rodig,2 Nicholas A. Cacalano,3 Maria Berg,1 Robert D. Schreiber,2 and Warren J. Leonard1,*

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-16741; Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 631102; and DNAX Research Institute, Palo Alto, California 943043

Received 11 February 1998/Returned for modification 20 March 1998/Accepted 14 August 1998

Phosphatidylinositol 3-kinase (PI 3-K) plays an important role in signaling via a wide range of receptors such as those for antigen, growth factors, and a number of cytokines, including interleukin-2 (IL-2). PI 3-K has been implicated in both IL-2-induced proliferation and prevention of apoptosis. A number of potential mechanisms for the recruitment of PI 3-K to the IL-2 receptor have been proposed. We now have found that tyrosine residues in the IL-2 receptor beta  chain (IL-2Rbeta ) are unexpectedly not required for the recruitment of the p85 component of PI 3-K. Instead, we find that Jak1, which associates with membrane-proximal regions of the IL-2Rbeta cytoplasmic domain, is essential for efficient IL-2Rbeta -p85 interaction, although some IL-2Rbeta -p85 association can be seen in the absence of Jak1. We also found that Jak1 interacts with p85 in the absence of IL-2Rbeta and that IL-2Rbeta and Jak1 cooperate for the efficient recruitment and tyrosine phosphorylation of p85. This is the first report of a PI 3-K-Jak1 interaction, and it implicates Jak1 in an essential IL-2 signaling pathway distinct from the activation of STAT proteins.

* Corresponding author. Mailing address: Laboratory of Molecular Immunology, Bldg. 10, Rm. 7N252, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674. Phone: (301) 496-0098. Fax: (301) 402-0971. E-mail: wjl{at}helix.nih.gov.

dagger Present address: DNAX Research Institute, Palo Alto, CA 94304.

Molecular and Cellular Biology, November 1998, p. 6416-6422, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hsu, C.-L., Kikuchi, K., Kondo, M. (2007). Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment. Blood 110: 1420-1428 [Abstract] [Full Text]  
  • Cipres, A., Carrasco, S., Merino, E., Diaz, E., Krishna, U. M., Falck, J. R., Martinez-A, C., Merida, I. (2003). Regulation of Diacylglycerol Kinase {alpha} by Phosphoinositide 3-Kinase Lipid Products. J. Biol. Chem. 278: 35629-35635 [Abstract] [Full Text]  
  • Lindemann, M. J., Benczik, M., Gaffen, S. L. (2003). Anti-apoptotic Signaling by the Interleukin-2 Receptor Reveals a Function for Cytoplasmic Tyrosine Residues within the Common gamma (gamma c) Receptor Subunit. J. Biol. Chem. 278: 10239-10249 [Abstract] [Full Text]  
  • Jiang, K., Zhong, B., Ritchey, C., Gilvary, D. L., Hong-Geller, E., Wei, S., Djeu, J. Y. (2003). Regulation of Akt-dependent cell survival by Syk and Rac. Blood 101: 236-244 [Abstract] [Full Text]  
  • Xue, H.-H., Kovanen, P. E., Pise-Masison, C. A., Berg, M., Radovich, M. F., Brady, J. N., Leonard, W. J. (2002). IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes. Proc. Natl. Acad. Sci. USA 99: 13759-13764 [Abstract] [Full Text]  
  • Oki, S., Limnander, A., Danial, N. N., Rothman, P. B. (2002). Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells. Blood 100: 966-973 [Abstract] [Full Text]  
  • Jones, D. R., Gonzalez-Garcia, A., Diez, E., Martinez-A., C., Carrera, A. C., Merida, I. (1999). The Identification of Phosphatidylinositol 3,5-bisphosphate in T-lymphocytes and Its Regulation by Interleukin-2. J. Biol. Chem. 274: 18407-18413 [Abstract] [Full Text]  
  • Gadina, M., Sudarshan, C., Visconti, R., Zhou, Y.-J., Gu, H., Neel, B. G., O'Shea, J. J. (2000). The Docking Molecule Gab2 Is Induced by Lymphocyte Activation and Is Involved in Signaling by Interleukin-2 and Interleukin-15 but Not Other Common gamma Chain-using Cytokines. J. Biol. Chem. 275: 26959-26966 [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»