Direct interaction between Kit and the interleukin-7 receptor.

In vivo analyses of thymopoiesis in mice defective in signaling through Kit and gammac or Kit and IL-7Ralpha demonstrate synergy and partial complementation of gammac or IL-7-mediated signaling by the Kit signaling pathway. Our molecular analysis in T-lymphoid cells as well as in nonhematopoietic cells shows that Kit and IL-7R ...
signaling pathways directly interact. KL-mediated activation of Kit induced strong tyrosine phosphorylation of gammac and IL-7Ralpha in the absence of IL-7. Activated Kit formed a complex with either IL-7Ralpha or gammac, and tyrosine phosphorylation of both subunits occurred independently of Jak3, suggesting that gammac and IL-7Ralpha are each direct substrates of Kit. Kit activated Jak3 in an IL-7R-dependent manner. Moreover, deficient Stat5 activation of the Kit mutant YY567/569FF lacking intrinsic Src activation capacity was partially reconstituted in the presence of IL-7R and Jak3. Based on the molecular data, we propose a model of Kit-mediated functional activation of gammac-containing receptors such as IL-7R, similar to the interaction between Kit and Epo-R. Such indirect activation of the Jak-Stat pathway induced by the interaction between an RTK and type I cytokine receptor could be the underlying mechanism for a context-specific signaling repertoire of a pleiotropic RTK-like Kit.
Mesh Terms:
Cells, Cultured, Cytoplasm, Humans, Immunoblotting, Immunoprecipitation, Interleukin Receptor Common gamma Subunit, Interleukin-7, Janus Kinase 3, Jurkat Cells, Kidney, Phosphorylation, Proto-Oncogene Proteins c-kit, Receptors, Interleukin-7, STAT5 Transcription Factor, Signal Transduction, Stem Cell Factor, Trans-Activators, Tyrosine
Blood
Date: Sep. 15, 2007
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