| First Author | Jahn T | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 6 | Pages | 1840-7 |
| PubMed ID | 17554063 | Mgi Jnum | J:146400 |
| Mgi Id | MGI:3837522 | Doi | 10.1182/blood-2005-12-028019 |
| Citation | Jahn T, et al. (2007) Direct interaction between Kit and the interleukin-7 receptor. Blood 110(6):1840-7 |
| abstractText | 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. |
