Referenced in: none

Automatically associated channels: Cav3.1

Title: Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells.

Authors: 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

Journal, date & volume: Mol. Cell, 2006 Dec 8 , 24, 665-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17157250

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.