Format

Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 2007 Sep 15;110(6):1840-7. Epub 2007 Jun 6.

Direct interaction between Kit and the interleukin-7 receptor.

Author information

  • 1Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA, USA. tjahn@stanford.edu

Abstract

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.

PMID:
17554063
[PubMed - indexed for MEDLINE]
PMCID:
PMC1976346
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk