Rat brain myo-inositol 3-phosphate synthase is a phosphoprotein
R N Parthasarathy1, J Lakshmanan, M Thangavel
1Molecular Neuroscience and Bioinformatics Laboratories, Mental Health, Behavioral Science and Research Services, Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA. ranga.parthasarathy@va.gov
Molecular and Cellular Biochemistry
|March 19, 2013
Summary
Researchers discovered that myo-inositol 3-phosphate synthase (IPS) can be phosphorylated at Serine-524, a novel finding potentially explaining lithium
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Lithium's therapeutic effects in bipolar disorder are not fully understood.
- Lithium modulates inositol signaling by inhibiting enzymes like myo-inositol 3-phosphate synthase (IPS).
Purpose of the Study:
- To investigate the post-translational modification of IPS.
- To identify the specific site and functional implications of IPS phosphorylation.
Main Methods:
- Phosphorylation analysis using lambda protein phosphatase, ProQ-Diamond staining, and Western blot.
- Mass spectrometry to identify phosphorylation sites.
- Generation of a phospho-specific antibody for IPS detection.
Main Results:
- Demonstrated that IPS can be phosphorylated, with Serine-524 (S524) identified as the phosphorylation site.
- Developed an antibody capable of distinguishing phosphorylated and non-phosphorylated IPS.
- Detected phosphorylated IPS in brain and testis, but not in the intestine due to an isoform variation.
Conclusions:
- IPS is monophosphorylated at S524, a modification that does not affect its enzymatic activity.
- Phosphorylated IPS (phospho-IPS) may have novel functions in the brain and other tissues.
- Further research is needed to elucidate the functional role of phospho-IPS in brain inositol signaling.
Related Concept Videos
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:48ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:18ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...