Cdc2/Cyclin B1 Interacts with and Modulates Inositol 1,4,5-Trisphosphate Receptor (Type 1) Functions

The resistance of inositol 1,4,5-trisphosphate receptor (IP3R)-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 IP3-gated Ca2+ release during apoptosis in...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-11, Vol.175 (9), p.6205-6210
Main Authors: Li, Xiaogui, Malathi, Krishnamurthy, Krizanova, Olga, Ondrias, Karol, Sperber, Kirk, Ablamunits, Vitaly, Jayaraman, Thottala
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis
Calcium - metabolism
Calcium Channels - physiology
Calcium Signaling
CDC2 Protein Kinase - physiology
Cyclin B - physiology
Cyclin B1
Humans
Inositol 1,4,5-Trisphosphate - metabolism
Inositol 1,4,5-Trisphosphate Receptors
Jurkat Cells
Molecular Sequence Data
Phosphorylation
Rats
Receptors, Cytoplasmic and Nuclear - physiology
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Summary:The resistance of inositol 1,4,5-trisphosphate receptor (IP3R)-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 IP3-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 Arg391, Arg441, and Arg871; 2) IP3R1 phosphorylation at Thr799 by the cdc2/CyB complex increases IP3 binding; and 3) cdc2/CyB phosphorylation increases IP3-gated Ca2+ release. Taken together, these results demonstrate that cdc2/CyB phosphorylation positively regulates IP3-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 inhibitor(s) may constitute a new therapy for the treatment of several human immune disorders.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.9.6205