Histidine Phosphorylation of the Potassium Channel KCa3.1 by Nucleoside Diphosphate Kinase B Is Required for Activation of KCa3.1 and CD4 T Cells

Shekhar Srivastava, Zhai Li, Kyung Ko, Papiya Choudhury, Mamdouh Albaqumi, Amanda K. Johnson, Ying Yan, Jonathan M. Backer, Derya Unutmaz, William A. Coetzee, Edward Y. Skolnik

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

The Ca2+-activated K+ channel KCa3.1 is required for Ca2+ influx and the subsequent activation of B and T cells. Inhibitors of KCa3.1 are in development to treat autoimmune diseases and transplant rejection, underscoring the importance in understanding how these channels are regulated. We show that nucleoside diphosphate kinase B (NDPK-B), a mammalian histidine kinase, functions downstream of PI(3)P to activate KCa3.1. NDPK-B directly binds and activates KCa3.1 by phosphorylating histidine 358 in the carboxyl terminus of KCa3.1. Endogenous NDPK-B is also critical for KCa3.1 channel activity and the subsequent activation of CD4 T cells. These findings provide one of the best examples whereby histidine phosphorylation regulates a biological process in mammals, and provide an example whereby a channel is regulated by histidine phosphorylation. The critical role for NDPK-B in the reactivation of CD4 T cells indicates that understanding NDPK-B regulation should uncover novel pathways required for T cell activation.

Original languageEnglish (US)
Pages (from-to)665-675
Number of pages11
JournalMolecular Cell
Volume24
Issue number5
DOIs
StatePublished - Dec 8 2006

Keywords

  • CELLIMMUNO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Srivastava, S., Li, Z., Ko, K., Choudhury, P., Albaqumi, M., Johnson, A. K., Yan, Y., Backer, J. M., Unutmaz, D., Coetzee, W. A., & Skolnik, E. Y. (2006). Histidine Phosphorylation of the Potassium Channel KCa3.1 by Nucleoside Diphosphate Kinase B Is Required for Activation of KCa3.1 and CD4 T Cells. Molecular Cell, 24(5), 665-675. https://doi.org/10.1016/j.molcel.2006.11.012