Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes.
Signaling through the T cell antigen receptor leading to elimination (negative selection) or differentiation (positive selection) of developing thymocytes generates a self-tolerant T cell repertoire. Here we report that the serine-threonine kinase MINK selectively connects the T cell receptor to a signaling pathway that mediates negative but not positive selection. Analysis of this pathway suggested that the essential function of MINK in the elimination of self-reactive thymocytes may be associated with 'downstream' activation of Jun kinase and enhancement of expression of the proapoptotic molecule Bim.
McCarty
Nami
N
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Paust
Silke
S
Ikizawa
Koichi
K
Dan
Ippeita
I
Li
Xiaoyan
X
Cantor
Harvey
H
D000818:Animals; D015536:Down-Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism
C092068:Kcne1 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D011948:Receptors, Antigen, T-Cell