Inositol 1,4,5-trisphosphate receptor (type 1) phosphorylation and modulation by Cdc2.
Calcium (Ca2+) release from the endoplasmic reticulum (ER) controls numerous cellular functions including proliferation, and is regulated in part by inositol 1,4,5-trisphosphate receptors (IP3Rs). IP3Rs are ubiquitously expressed intracellular Ca2+-release channels found in many cell types. Although IP3R-mediated Ca2+ release has been implicated in cellular proliferation, the biochemical pathways that modulate intracellular Ca2+ release during cell cycle progression are not known. Sequence analysis of IP3R1 reveals the presence of two putative phosphorylation sites for cyclin-dependent kinases (cdks). In the present study, we show that cdc2/CyB, a critical regulator of eukaryotic cell cycle progression, phosphorylates IP3R1 in vitro and in vivo at both Ser(421) and Thr(799) and that this phosphorylation increases IP3 binding. Taken together, these results indicate that IP3R1 may be a specific target for cdc2/CyB during cell cycle progression.
Malathi
Krishnamurthy
K
Vascular Biology Laboratory, Department of Medicine, St. Luke's Roosevelt Hospital Center, New York, New York, USA.
Kohyama
Shinya
S
Ho
Michael
M
Soghoian
Damien
D
Li
Xiaogui
X
Silane
Michael
M
Berenstein
Alejandro
A
Jayaraman
Thottala
T
D000595:Amino Acid Sequence; D000818:Animals; D045163:Antibodies, Phospho-Specific / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019169:Jurkat Cells; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
D045163:Antibodies, Phospho-Specific; D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013912:Threonine; D012694:Serine; D015544:Inositol 1,4,5-Trisphosphate; D016203:CDC2 Protein Kinase; D002118:Calcium