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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1840-1847. Prepublished online as a Blood First Edition Paper on June 6, 2007; DOI 10.1182/blood-2005-12-028019. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2005-12-028019v1 110/6/1840    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jahn, T. Articles by Weinberg, K. Search for Related Content PubMed PubMed Citation Articles by Jahn, T. Articles by Weinberg, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 29, 2005 Accepted June 1, 2007 Direct interaction between Kit and the interleukin-7 receptor Thomas Jahn*, Simran Sindhu, Stacie Gooch, Petra Seipel, Philip Lavori, Erica Leifheit, and Kenneth Weinberg Division of Research Immunology & Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA Dept of Health Research and Policy – Biostatistics, Stanford University School of Medicine, Stanford, CA Division of Stem Cell Transplantation, Dept of Pediatrics, Stanford University School of Medicine, Stanford, CA * Corresponding author; email: tjahn{at}stanford.edu. In vivo analyses of thymopoiesis in mice defective in signaling through Kit and c or Kit and IL-7R demonstrate synergy and partial complementation of c or IL-7-mediated signaling by the Kit signaling pathway. Our molecular analysis in T-lymphoid cells as well as in non-hematopoietic cells shows that Kit and IL-7R signaling pathways directly interact. KL-mediated activation of Kit induced strong tyrosine phosphorylation of c and IL-7R in the absence of IL-7. Activated Kit formed a complex with either IL-7R or c, and tyrosine phosphorylation of both subunits occurred independently of Jak3, suggesting that c and IL-7R 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 c-containing receptors like 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Buza-Vidas, M. Cheng, S. Duarte, H. Nozad Charoudeh, S. E. W. Jacobsen, and E. Sitnicka FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells Blood, April 9, 2009; 113(15): 3453 - 3460. [Abstract] [Full Text] [PDF] C. T. Jensen, C. Boiers, S. Kharazi, A. Lubking, T. Ryden, M. Sigvardsson, E. Sitnicka, and S. E. W. Jacobsen Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development Blood, February 15, 2008; 111(4): 2083 - 2090. [Abstract] [Full Text] [PDF]

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