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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.


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