Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions

Xiaogui Li, Krishnamurthy Malathi, Olga Krizanova, Karol Ondrias, Kirk Sperber, Vitaly Ablamunits, Thottala Jayaraman

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The resistance of inositol 1,4,5-trisphosphate receptor (IP 3R)-deficient cells to multiple forms of apoptosis demonstrates the importance of IP3-gated calcium (Ca2+) release to cellular apoptosis. However, the specific upstream biochemical events leading to IP 3-gated Ca2+ release during apoptosis induction are not known. We have shown previously that the cyclin-dependent kinase 1/cyclin B (cdk1/CyB or cdc2/CyB) complex phosphorylates IP3R1 in vitro and in vivo at Ser421 and Thr799. In this study, we show that: 1) the cdc2/CyB complex directly interacts with IP3R1 through Arg 391, Arg441, and Arg871; 2) IP3R1 phosphorylation at Thr799 by the cdc2/CyB complex increases IP 3 binding; and 3) cdc2/CyB phosphorylation increases IP 3-gated Ca2+ release. Taken together, these results demonstrate that cdc2/CyB phosphorylation positively regulates IP 3-gated Ca2+ signaling. In addition, identification of a CyB docking site(s) on IP3R1 demonstrates, for the first time, a direct interaction between a cell cycle component and an intracellular calcium release channel. Blocking this phosphorylation event with a specific peptide in inhibitor(s) may constitute a new therapy for the treatment of several human immune disorders.

Original languageEnglish
Pages (from-to)6205-6210
Number of pages6
JournalJournal of Immunology
Issue number9
StatePublished - 1 Nov 2005


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