High impact information on ITPKB

• Inositol-1,4,5-trisphosphate 3-kinases (IP3K) A, B, and C as well as inositol polyphosphate multikinase (IPMK) catalyze the first step in the formation of the higher phosphorylated inositols InsP5 and InsP6 by metabolizing Ins(1,4,5)P3 to Ins(1,3,4,5)P4 [1].
• Mutagenesis studies revealed that both the calmodulin binding and the InsP3 binding domain in IP3K are involved in inhibitor binding [1].
• Complete inhibition of Ins(1,4,5)P(3) 3-kinase (IP3K) by either adriamycin or its specific antibody blocked Ca(2+) oscillations [2].
• Control of oxidative stress resistance by IP3 kinase in Drosophila melanogaster [3].
• Among them, Type B inositol 1,4,5-trisphosphate 3-kinase (ITPKB), and regulator of G protein signaling 4 (RGS4) showed highly altered expression levels in patients (P values < 0.0001) [4].

Biological context of ITPKB

• 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 [5].
• For the endogenous enzyme, we confirmed both actin and endoplasmic reticulum localization by employing a high affinity antibody against IP3K-B [6].
• 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].
• Ins(1,4,5)P(3) 3-kinase (IP3K) phosphorylates the Ca(2+)-mobilizing second messenger Ins(1,4,5)P(3) to yield the putative second messenger Ins(1,3,4,5)P(4) [8].
• We previously reported the isolation of a rat cDNA clone encoding a protein with significant sequence homology to the B isoform of human myo-inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase B); this protein was thus designated rat IP3 3-kinase B [Thomas, Brake, Luzio, Stanley and Banting (1994) Biochim. Biophys. Acta 1220, 219-222] [9].

Anatomical context of ITPKB

• 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 [10].
• We also used deconvolution microscopy to visualize the relationship between F-actin and endoplasmic reticulum inside dendritic spines, revealing a delicate microorganization of IP3K near the Ca(2+) stores [7].
• IP3K was intensely concentrated as puncta in spine heads when Ca(2+) influx was low, but rapidly and reversibly redistributed to a striated morphology in the main dendrite when Ca(2+) influx was high [7].
• Effects of elevated expression of inositol 1,4,5-trisphosphate 3-kinase B on Ca2+ homoeostasis in HeLa cells [8].
• The fact that IP3 3-kinase B is localized exclusively to membranes of Ca2+ stores, is consistent with a model where this kinase plays a role in IP3-dependent Ca2+ release [9].

Associations of ITPKB with chemical compounds

• [Dewaste, Moreau, De Smedt, Bex, De Smedt, Wuytaack, Missiaen and Erneux (2003) Biochem. J. 374, 41-49] showed that over-expressed EGFP (enhanced green fluorescent protein) fused to Ins(1,4,5)P3 3-kinase B (IP3K-B) co-localizes with the cytoskeleton, as well as with the endoplasmic reticulum and the plasma membrane [6].
• Direct interaction of this actin-binding segment with only F-actin, but not with G-actin, was observed in vitro using a bacterially expressed, affinity-purified GST (glutathione S-transferase)-Rattus norvegicus IP3K (aa 108-170) fusion protein [6].
• On stimulation with a supramaximal dose of histamine, 67% of cells induced to express IP3KB gave no detectable elevation in cytosolic Ca(2+), compared with 3% of uninduced cells [8].
• However, no IP3 kinase isoform had been shown to generate the physiologically important isoform of inositol tetrakisphosphate, i.e. inositol 1,3,4,5-tetrakisphosphate [9].

References