Protein kinase A and two phosphatases are components of the inositol 1,4,5-trisphosphate receptor macromolecular signaling complex.
The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed intracellular calcium (Ca(2+)) release channel on the endoplasmic reticulum. IP3Rs play key roles in controlling Ca(2+) signals that activate numerous cellular functions including T cell activation, neurotransmitter release, oocyte fertilization and apoptosis. There are three forms of IP3R, all of which are ligand-gated channels activated by the second messenger inositol 1,4,5-trisphosphate. Channel function is modulated via cross-talk with other signaling pathways including those mediated by kinases and phosphatases. In particular IP3Rs are known to be regulated by cAMP-dependent protein kinase (PKA) phosphorylation. In the present study we show that PKA and the protein phosphatases PP1 and PP2A are components of the IP3R1 macromolecular signaling complex. PKA phosphorylation of IP3R1 increases channel activity in planar lipid bilayers. These studies indicate that regulation of IP3R1 function via PKA phosphorylation involves components of a macromolecular signaling complex.
DeSouza
Nikhil
N
Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Reiken
Steven
S
Ondrias
Karol
K
Yang
Yi-Ming
YM
Matkovich
Scot
S
Marks
Andrew R
AR
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002531:Cerebellum / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015151:Immunoblotting; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D008051:Lipid Bilayers; D008840:Microfilament Proteins; D009865:Oocytes / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
C112986:AIF1 protein, human; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D008051:Lipid Bilayers; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium