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Publication : Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold.

First Author  Raman V Year  2001
Journal  J Immunol Volume  167
Issue  11 Pages  6270-8
PubMed ID  11714790 Mgi Jnum  J:72830
Mgi Id  MGI:2153664 Doi  10.4049/jimmunol.167.11.6270
Citation  Raman V, et al. (2001) Requirement for Ca(2+)/Calmodulin-Dependent Kinase Type IV/Gr in Setting the Thymocyte Selection Threshold. J Immunol 167(11):6270-8
abstractText  The outcome of thymocyte selection is influenced by the nature of Ca(2+) signals transduced by the TCR. Robust Ca(2+) responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca(2+) signals, we examined selection events in mice lacking Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca(2+)-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.
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