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. 2000 Nov 1;351(Pt 3):551–555.

Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase.

X Yang 1, S B Shears 1
PMCID: PMC1221393  PMID: 11042108

Abstract

We describe a human cDNA encoding 1-kinase activity that inactivates Ins(3,4,5,6)P(4), an inhibitor of chloride-channel conductance that regulates epithelial salt and fluid secretion, as well as membrane excitability. Unexpectedly, we further discovered that this enzyme has alternative positional specificity (5/6-kinase activity) towards a different substrate, namely Ins(1,3,4)P(3). Kinetic data from a recombinant enzyme indicate that Ins(1,3,4)P(3) (K(m)=0.3 microM; V(max)=320 pmol/min per microg) and Ins(3,4,5,6)P(4) (K(m)=0.1 microM; V(max)=780 pmol/min per microg) actively compete for phosphorylation in vivo. This competition empowers the kinase with multitasking capability in several key aspects of inositol phosphate signalling.

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Selected References

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  1. Abdullah M., Hughes P. J., Craxton A., Gigg R., Desai T., Marecek J. F., Prestwich G. D., Shears S. B. Purification and characterization of inositol-1,3,4-trisphosphate 5/6-kinase from rat liver using an inositol hexakisphosphate affinity column. J Biol Chem. 1992 Nov 5;267(31):22340–22345. [PubMed] [Google Scholar]
  2. Carew M. A., Yang X., Schultz C., Shears S. B. myo-inositol 3,4,5,6-tetrakisphosphate inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell line. J Biol Chem. 2000 Sep 1;275(35):26906–26913. doi: 10.1074/jbc.M002316200. [DOI] [PubMed] [Google Scholar]
  3. Field J., Wilson M. P., Mai Z., Majerus P. W., Samuelson J. An Entamoeba histolytica inositol 1,3,4-trisphosphate 5/6-kinase has a novel 3-kinase activity. Mol Biochem Parasitol. 2000 Apr 30;108(1):119–123. doi: 10.1016/s0166-6851(00)00197-3. [DOI] [PubMed] [Google Scholar]
  4. Frings S., Reuter D., Kleene S. J. Neuronal Ca2+ -activated Cl- channels--homing in on an elusive channel species. Prog Neurobiol. 2000 Feb;60(3):247–289. doi: 10.1016/s0301-0082(99)00027-1. [DOI] [PubMed] [Google Scholar]
  5. Hughes P. J., Hughes A. R., Putney J. W., Jr, Shears S. B. The regulation of the phosphorylation of inositol 1,3,4-trisphosphate in cell-free preparations and its relevance to the formation of inositol 1,3,4,6-tetrakisphosphate in agonist-stimulated rat parotid acinar cells. J Biol Chem. 1989 Nov 25;264(33):19871–19878. [PubMed] [Google Scholar]
  6. Hughes P. J., Kirk C. J., Michell R. H. Inhibition of porcine brain inositol 1,3,4-trisphosphate kinase by inositol polyphosphates, other polyol phosphates, polyanions and polycations. Biochim Biophys Acta. 1994 Aug 11;1223(1):57–70. doi: 10.1016/0167-4889(94)90073-6. [DOI] [PubMed] [Google Scholar]
  7. Irvine R. F. Is inositol tetrakisphosphate the second messenger that controls Ca2+ entry into cells? Adv Second Messenger Phosphoprotein Res. 1992;26:161–185. [PubMed] [Google Scholar]
  8. Ismailov I. I., Fuller C. M., Berdiev B. K., Shlyonsky V. G., Benos D. J., Barrett K. E. A biologic function for an "orphan" messenger: D-myo-inositol 3,4,5,6-tetrakisphosphate selectively blocks epithelial calcium-activated chloride channels. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10505–10509. doi: 10.1073/pnas.93.19.10505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. King W. G., Downes C. P., Prestwich G. D., Rittenhouse S. E. Ca2(+)-stimulatable and protein kinase C-inhibitable accumulation of inositol 1,3,4,6-tetrakisphosphate in human platelets. Biochem J. 1990 Aug 15;270(1):125–131. doi: 10.1042/bj2700125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Large W. A., Wang Q. Characteristics and physiological role of the Ca(2+)-activated Cl- conductance in smooth muscle. Am J Physiol. 1996 Aug;271(2 Pt 1):C435–C454. doi: 10.1152/ajpcell.1996.271.2.C435. [DOI] [PubMed] [Google Scholar]
  11. Menniti F. S., Oliver K. G., Nogimori K., Obie J. F., Shears S. B., Putney J. W., Jr Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate. J Biol Chem. 1990 Jul 5;265(19):11167–11176. [PubMed] [Google Scholar]
  12. Odom A. R., Stahlberg A., Wente S. R., York J. D. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science. 2000 Mar 17;287(5460):2026–2029. doi: 10.1126/science.287.5460.2026. [DOI] [PubMed] [Google Scholar]
  13. Saiardi A., Caffrey J. J., Snyder S. H., Shears S. B. Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett. 2000 Feb 18;468(1):28–32. doi: 10.1016/s0014-5793(00)01194-7. [DOI] [PubMed] [Google Scholar]
  14. Saiardi A., Erdjument-Bromage H., Snowman A. M., Tempst P., Snyder S. H. Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr Biol. 1999 Nov 18;9(22):1323–1326. doi: 10.1016/s0960-9822(00)80055-x. [DOI] [PubMed] [Google Scholar]
  15. Shears S. B. The versatility of inositol phosphates as cellular signals. Biochim Biophys Acta. 1998 Dec 8;1436(1-2):49–67. doi: 10.1016/s0005-2760(98)00131-3. [DOI] [PubMed] [Google Scholar]
  16. Tan Z., Bruzik K. S., Shears S. B. Properties of the inositol 3,4,5,6-tetrakisphosphate 1-kinase purified from rat liver. Regulation of enzyme activity by inositol 1,3,4-trisphosphate. J Biol Chem. 1997 Jan 24;272(4):2285–2290. doi: 10.1074/jbc.272.4.2285. [DOI] [PubMed] [Google Scholar]
  17. Vajanaphanich M., Schultz C., Rudolf M. T., Wasserman M., Enyedi P., Craxton A., Shears S. B., Tsien R. Y., Barrett K. E., Traynor-Kaplan A. Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. Nature. 1994 Oct 20;371(6499):711–714. doi: 10.1038/371711a0. [DOI] [PubMed] [Google Scholar]
  18. Wilson M. P., Majerus P. W. Characterization of a cDNA encoding Arabidopsis thaliana inositol 1,3,4-trisphosphate 5/6-kinase. Biochem Biophys Res Commun. 1997 Mar 27;232(3):678–681. doi: 10.1006/bbrc.1997.6355. [DOI] [PubMed] [Google Scholar]
  19. Wilson M. P., Majerus P. W. Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme. J Biol Chem. 1996 May 17;271(20):11904–11910. doi: 10.1074/jbc.271.20.11904. [DOI] [PubMed] [Google Scholar]
  20. Xie W., Kaetzel M. A., Bruzik K. S., Dedman J. R., Shears S. B., Nelson D. J. Inositol 3,4,5,6-tetrakisphosphate inhibits the calmodulin-dependent protein kinase II-activated chloride conductance in T84 colonic epithelial cells. J Biol Chem. 1996 Jun 14;271(24):14092–14097. doi: 10.1074/jbc.271.24.14092. [DOI] [PubMed] [Google Scholar]
  21. Xie W., Solomons K. R., Freeman S., Kaetzel M. A., Bruzik K. S., Nelson D. J., Shears S. B. Regulation of Ca2+-dependent Cl- conductance in a human colonic epithelial cell line (T84): cross-talk between Ins(3,4,5,6)P4 and protein phosphatases. J Physiol. 1998 Aug 1;510(Pt 3):661–673. doi: 10.1111/j.1469-7793.1998.661bj.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yang X., Rudolf M., Carew M. A., Yoshida M., Nerreter V., Riley A. M., Chung S. K., Bruzik K. S., Potter B. V., Schultz C. Inositol 1,3,4-trisphosphate acts in vivo as a specific regulator of cellular signaling by inositol 3,4,5,6-tetrakisphosphate. J Biol Chem. 1999 Jul 2;274(27):18973–18980. doi: 10.1074/jbc.274.27.18973. [DOI] [PubMed] [Google Scholar]

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