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

116 Citations (Scopus)

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

Fingerprint

NM23 Nucleoside Diphosphate Kinases
Potassium Channels
Histidine
Phosphorylation
T-Lymphocytes
Biological Phenomena
Calcium-Activated Potassium Channels
Graft Rejection
Autoimmune Diseases
Mammals
B-Lymphocytes

Keywords

  • CELLIMMUNO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Histidine Phosphorylation of the Potassium Channel KCa3.1 by Nucleoside Diphosphate Kinase B Is Required for Activation of KCa3.1 and CD4 T Cells. / Srivastava, Shekhar; Li, Zhai; Ko, Kyung; Choudhury, Papiya; Albaqumi, Mamdouh; Johnson, Amanda K.; Yan, Ying; Backer, Jonathan M.; Unutmaz, Derya; Coetzee, William A.; Skolnik, Edward Y.

In: Molecular Cell, Vol. 24, No. 5, 08.12.2006, p. 665-675.

Research output: Contribution to journalArticle

Srivastava, S, Li, Z, Ko, K, Choudhury, P, Albaqumi, M, Johnson, AK, Yan, Y, Backer, JM, Unutmaz, D, Coetzee, WA & Skolnik, EY 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, vol. 24, no. 5, pp. 665-675. https://doi.org/10.1016/j.molcel.2006.11.012
Srivastava, Shekhar ; Li, Zhai ; Ko, Kyung ; Choudhury, Papiya ; Albaqumi, Mamdouh ; Johnson, Amanda K. ; Yan, Ying ; Backer, Jonathan M. ; Unutmaz, Derya ; Coetzee, William A. ; Skolnik, Edward Y. / Histidine Phosphorylation of the Potassium Channel KCa3.1 by Nucleoside Diphosphate Kinase B Is Required for Activation of KCa3.1 and CD4 T Cells. In: Molecular Cell. 2006 ; Vol. 24, No. 5. pp. 665-675.
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