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JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of
phosphatidylinositol-3' kinase
N Sharfe, HK Dadi and CM Roifman
Division of Immunology and Allergy, Hospital for Sick Children, University
of Toronto, Ontario, Canada.
The interleukin-7 (IL-7) receptor is expressed throughout T-cell
differentiation and, although lacking a tyrosine kinase domain, mediates
tyrosine phosphorylation in T cells. We have identified IL-7- induced
activation of three cyoplasmic tyrosine kinases in T cells, Jak1, Jak3, and
the src-like kinase p56lck. Many members of the cytokine receptor
superfamily activate the Jak protein tyrosine kinase family, with resultant
phosphorylation of the Stat transcriptional activator factors. We describe
here a novel function of the Jak kinases, because Jak kinase activity is
not only required for Stat activation but also for P13 kinase response to
IL-7 in human T cells. We show that IL-7 receptor-mediated Jak activation
can occur independently of p56lck activity. IL-7-induced P13 kinase
activation, mediated by tyrosine phosphorylation of the P13 kinase p85
subunit, is essential to the IL-7 proliferative signal and also occurs in
the absence of src family kinase activity. Jak3 is found associated with
the p85 subunit of P13 kinase in an IL-7-responsive manner in T cells and
appears to regulate IL-7-induced P13 kinase activation by mediating
tyrosine phosphorylation of the p85 subunit. Specific inhibition of IL-
7-induced Jak kinase activity ablates p85 tyrosine phosphorylation,
subsequent P13 kinase activation, and, ultimately, proliferation. The
ability to regulate P13 kinase activity indicates a more generalized role
for the Jak family than activation of gene transcription via the Stat
family in cytokine receptor signal transduction.
Volume 86,
Issue 6,
pp. 2077-2085,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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