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 language | English (US) |
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Pages (from-to) | 665-675 |
Number of pages | 11 |
Journal | Molecular Cell |
Volume | 24 |
Issue number | 5 |
DOIs | |
State | Published - Dec 8 2006 |
Keywords
- CELLIMMUNO
- MOLNEURO
- SIGNALING
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology