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Molecular and Cellular Biology, November 1998, p. 6416-6422, Vol. 18, No. 11
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
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Functional Cooperation of the Interleukin-2 Receptor
Chain
and Jak1 in Phosphatidylinositol 3-Kinase Recruitment and
Phosphorylation

chain
(IL-2R
) 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-2R
cytoplasmic domain, is
essential for efficient IL-2R
-p85 interaction, although some
IL-2R
-p85 association can be seen in the absence of Jak1. We also
found that Jak1 interacts with p85 in the absence of IL-2R
and that
IL-2R
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.
Present address: DNAX Research Institute, Palo Alto, CA 94304.
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