Disease relevance of C04520

• In addition to its effects on phosphoinositides, SigD has been shown to convert inositol 1,3,4,5,6-pentakisphosphate (IP(5)) into inositol 1,4,5,6-tetrakisphosphate (IP(4)), and the latter has been postulated to mediate the diarrhea caused by Salmonella [1].

High impact information on C04520

• Synthesis of inositol 1,4,5,6-tetrakisphosphate, but not IP6, was required for gene regulation through ArgR-Mcm1 [2].
• Oscillatory chloride efflux at the pollen tube apex has a role in growth and cell volume regulation and is targeted by inositol 3,4,5,6-tetrakisphosphate [3].
• A transient rise in cellular inositol 1,4,5,6-tetrakisphosphate was also observed and was accompanied by increased chloride channel activity [4].
• Moreover, HeLa cells infected with S. dublin SB c/s do not accumulate high levels of inositol 1,4,5,6-tetrakisphosphate that are characteristic of wild-type S. dublin-infected cells [5].
• Although PTEN M-CBR3 is a 3-phosphatase, levels of myo-inositol 1,4,5,6-tetrakisphosphate were not increased, whereas myo-inositol 1,3,4,6-tetrakisphospate levels increased by 80% [6].

Biological context of C04520

• The signal encoded by inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P(4)] antagonized pollen tube growth, induced cell volume increases, and disrupted Cl(-) efflux [3].
• Inositol 3,4,5,6-tetrakisphosphate was a more potent inhibitor of 3-phosphatase (IC50 about 10 microM) and did not affect 5-phosphatase [7].
• myo-Inositol 1,4,5,6-tetrakisphosphate and myo-inositol 3,4,5,6-tetrakisphosphate, two second messengers that may act as pH-dependent molecular switches [8].
• The Ins 1,3,4,5-P4 binding protein displayed high selectivity for Ins 1,3,4,5-P4 over other inositol-phosphates (IC50 for Ins 1,4,5,6-P4 150 nM, for Ins-P6 1 microM and for Ins 1,3,4-P3 5 microM) [9].

Anatomical context of C04520

• The mechanism by which inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5, 6)P4) regulates chloride (Cl-) secretion was evaluated in the colonic epithelial cell line T84 using whole cell voltage clamp techniques [10].
• Chicken erythrocytes labeled with [3H]inositol also contained high levels of Ins-1,3,4,6-P4 and Ins-3,4,5,6-P4, as well as InsP5, but only small amounts of Ins-1,3,4,5-P4 [11].
• Ca2+ influx evoked by inositol-3,4,5,6-tetrakisphosphate in ras-transformed NIH/3T3 fibroblasts [12].

Associations of C04520 with other chemical compounds

• Bombesin stimulated the net breakdown of inositol 1,3,4,5,6-pentakisphosphate and increased the level of inositol 3,4,5,6-tetrakisphosphate; the relative specific radioactivities of these two compounds were similar under all conditions [13].
• Inositol 1,3,4-trisphosphate kinase activity was potently inhibited by inositol 3,4,5,6-tetrakisphosphate (IC50 = 0.1-0.2 microM), which leads us to propose that inositol 3,4,5,6-tetrakisphosphate is an endogenous inhibitor of the kinase [14].
• The erythrocytes of the three bird species contained low levels of inositol-3,4,5,6-tetrakisphosphate and inositol-1,3,4,6-tetrakisphosphate, thought to be precursors of Ins(1,3,4,5,6)P(5) [15].
• Other inositol phosphates (inositol 1-monophosphate, inositol 1,4,5,6-tetrakisphosphate, inositol 1,3,4,5,6-pentakisphosphate and inositol 1,2,3,4,5,6-hexakisphosphate), tested in vitro, did not significantly influence LH release [16].

Gene context of C04520

• SigD activates Akt in epithelial cells and indirectly activates Cdc42 through one of its products, inositol 1,4,5,6-tetrakisphosphate [17].
• Herein we show that INO-4995, a synthetic analog of the intracellular signaling molecule, D-myo-inositol 3,4,5,6-tetrakisphosphate, inhibits Na(+) and fluid absorption across CF airway epithelia, thus alleviating this critical pathology [18].
• Inositol polyphosphate multikinase regulates inositol 1,4,5,6-tetrakisphosphate [19].
• However, CLCA-mediated Cl(-) secretion is transient, due in part to the inhibitory effects of myo-inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P(4)] [20].

Analytical, diagnostic and therapeutic context of C04520

• We now report that the recombinant human protein can catalyze the conversion of inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4) to Ins(1,3,4,5,6)P5 in vitro; the reaction product was identified by HPLC to be Ins(1,3,4,5,6)P5 [19].
• In contrast, microinjection of inositol 1-phosphate, inositol 1,4-biphosphate, and inositol 1,4,5,6-tetrakisphosphate did not induce changes in [Ca2+]i. Incubation in low-Ca2+ solution, or in the presence of L-type Ca2+ channel blockers did not affect InsP3-induced release of cytosolic Ca2+ [21].

References