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Inositol 1,4,5-trisphosphate receptor is phosphorylated by cyclic AMP-dependent protein kinase at serines 1755 and
C D Ferris1, A M Cameron, D S Bredt
1Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Abstract:
IP3 activates intracellular calcium release by binding to an intracellular ligand gated calcium permeable channel which has been shown to be regulated by protein kinase A phosphorylation. Two consensus sequences for protein kinase A phosphorylation are predicted by the recently isolated cDNA of the mouse and rat. In the present study we have isolated and sequenced the two peptides in the rat IP3 receptor which are phosphorylated by protein kinase A and demonstrate protein kinase A phosphorylation on S-1755 and S-1589.
Insights
Inositol trisphosphate (IP3) receptors are regulated by protein kinase A (PKA) phosphorylation. This study identifies specific sites, S-1755 and S-1589, on the rat IP3 receptor that are phosphorylated by PKA.
Area of Science:
- Molecular biology
- Cell signaling
- Biochemistry
Background:
- Inositol trisphosphate (IP3) triggers intracellular calcium release by binding to IP3 receptors.
- Protein kinase A (PKA) phosphorylation is known to regulate IP3 receptor activity.
- Previous studies predicted PKA phosphorylation sites in mouse and rat IP3 receptor cDNA.
Purpose of the Study:
- To identify and characterize the specific sites on the rat IP3 receptor phosphorylated by PKA.
- To confirm the predicted PKA phosphorylation consensus sequences in the rat IP3 receptor.
Main Methods:
- Isolation and sequencing of peptides from the rat IP3 receptor.
- In vitro phosphorylation assays using PKA.
- Mass spectrometry to identify phosphorylated residues.
Main Results:
- Two specific peptides within the rat IP3 receptor were identified as being phosphorylated by PKA.
- Phosphorylation by PKA was confirmed at serine residues S-1755 and S-1589.
- These sites correspond to the predicted PKA phosphorylation consensus sequences.
Conclusions:
- Serine residues S-1755 and S-1589 are key sites for PKA-mediated phosphorylation of the rat IP3 receptor.
- This phosphorylation likely plays a role in regulating intracellular calcium release.
- Further research can explore the functional consequences of PKA phosphorylation at these sites.