Disease relevance of ITPKA

• Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma [1].

High impact information on ITPKA

• D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism [2].
• We identified chlorogenic acid as a specific IPMK inhibitor whereas the flavonoids myricetin, 3',4',7,8-tetrahydroxyflavone and EGCG inhibit preferentially IP3K-A and IP3K-C [3].
• In order to clarify the special role of these InsP3 phosphorylating enzymes and of subsequent anabolic inositol phosphate reactions, a search was conducted for potent enzyme inhibitors starting with a fully active IP3K-A catalytic domain [3].
• Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus [4].
• The cyclic AMP-dependent protein kinase phosphorylated the inositol 1,4,5-trisphosphate 3-kinase A to the extent of 0.9 mol/mol and isoform B to 1 mol/mol [5].

Biological context of ITPKA

• Localization of the genes for human inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) and B (ITPKB) to chromosome regions 15q14-q21 and 1q41-q43, respectively, by in situ hybridization [6].
• These data suggest that ITPKA may be related to carcinogenesis by the modulation of inositol polyphosphates and Ca2+ homeostasis and that ITPKA may be a potential novel molecular target, biomarker, parameter, or all of these of cellular differentiation and of intracellular Ca2+ homeostatic characteristics in clinical medicine [1].
• We have used fixed and live-cell imaging in rat primary hippocampal cultures to characterize the synaptic dynamics of the F-actin binding protein inositol trisphosphate 3-kinase A (IP3K), which is localized in the spines of pyramidal neurons derived from the CA1 region [7].

Anatomical context of ITPKA

• Whereas predominant targeting to the cytoskeleton and endoplasmic reticulum has been shown for IP3K-A and IP3K-B, rat IP3K-C shuttles actively between the nucleus and cytoplasm [8].
• Western blots revealed dramatically down-regulated ITPKA expression in all OSCC cell lines examined [1].

Associations of ITPKA with chemical compounds

• ITPKA phosphorylates inositol 1,4,5-trisphosphate, which regulates the calcium (Ca2+) level within the cell by releasing Ca2+ from intracellular stores, and is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling [1].

Analytical, diagnostic and therapeutic context of ITPKA

• Immunohistochemistry analysis showed that 40 of 100 OSCC clinical samples had a significant decrease in ITPKA [1].
• Real-time quantitative reverse transcriptase-polymerase chain reaction showed down-regulated ITPKA mRNA expression in nine of 12 (75%) OSCC cell lines [1].

References