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D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis

One of the numerous cytosolic inositol polyphosphates that serve special fiunctions in the cell, : CPD-178 has been characterized as a receptor-generated negative intracellular regulator of one or more types of apical : CA+2-activated chloride channels (CaCCs) in epithelial cells , and specifically of the ClC-3 chloride channel, which is involved in tumor cell migration, apoptosis, and inflammatory responses . Elevated cytosolic : CA+2 activates CaCC phosphorylation by Ca2+/calmodulin-activated kinase II (CaMKII), increasing the sensitivity of CaCC to Ca2+-triggered opening, and sometimes triggers CaCC opening in some other manner as well. : CPD-178 is normally present in cells at a concentration of about 1 μM. However, its concentration slowly increases during sustained stimulation of G-protein-coupled receptors that activate phospholipase C and elevate cytosolic : CA+2 . As its concentration rises into the 3?10 μM range, : CPD-178 progressively inhibits the : CA+2-triggered opening of CaCC . The stimulated increase in the concentration of : CPD-178 appears to be a result of 1-dephosphorylation of : CPD-1107, a molecule that is relatively abundant in cells and has no effect on CaCC function. Inactivation is achieved by phosphorylation back to : CPD-1107. Remarkably, these two reactions are carried out by the same enzyme, : HS02123-MONOMER, which is also responsible for the phosphorylation of an earlier intermediate in the pathway, : INOSITOL-1-3-4-TRIPHOSPHATE . The versatility of the enzyme, which can phosphorylate its substrate at different positions, arise from the fact that substrates can approach the active site in up to three different orientations . Increased expression of : HS02123-MONOMER enhanced the receptor-activated : CPD-178 accumulation, as well as the responsiveness of cells to : CPD-178-mediated negative regulation of CaCC .

from BIOCYC source record: HUMAN_PWY-6365
Type: pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
BSID:
545329

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