Direct interaction between Kit and the interleukin-7 receptor
Direct interaction between Kit and the interleukin-7 receptor
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DOI：
10.1182/blood-2005-12-028019
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
Weinberg, Kenneth
中科院分区：
文献类型：
--
作者：
Jahn, Thomas;Sindhu, Simran;Weinberg, Kenneth
In vivo analyses of thymopoiesis in mice defective in signaling through Kit and gamma c or Kit and IL-7R alpha demonstrate synergy and partial complementation of gamma c 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 gamma c and IL-7R alpha in the absence of IL-7. Activated Kit formed a complex with either IL-7Ra or gamma c, and tyrosine phosphorylation of both subunits occurred independently of Jak3, suggesting that gamma c and IL-7Ra 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 gamma c-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.
