Inositol polyphosphates

Oculocerebrorenal syndrome, 30900 OCRL-1, an inositol polyphosphate 5-phosphatase... 

The inositol polyphosphate 5-phosphatases belong to a family of enzymes that terminate the signals generated by inositol lipid kinases and PLC. To date, two major types of 5-phosphatase have been identified, both of which share a common 5-phosphatase domain of approximately 300 amino acids, with several highly conserved motifs. Type-I enzymes are 43-65 kDa and preferentially hydrolyze 1(1,4,5)P3 and 1(1,3,4,5)P4, with the attendant formation of I(1,4)P2 and 1(1,3,4)P3, but have little or no activity towards membrane-bound phosphoinositides. The pro-totypic form of a type-15-phosphatase is a 43 kDa protein that is post-translationally modified by farnesylation of the carboxyl terminus CAAX motif this modification juxtaposes the enzyme with the membrane. Type-II enzymes are larger (75-160 kDa) and will hydrolyze both water-soluble inositol phosphates and lipids that... 

FIGURE 20-7 Pathways of inositol phosphate metabolism. Note that the metabolism of the second messenger I(1,4,5)P3 is shown to the left of the dashed line, while the interconversions of the higher inositol phosphates are shown to the right of the dashed line. Only the quantitatively major established pathways are depicted. Li+ is known to block the dephosphorylation reactions indicated by the (black) bars. Numbers refer to the following enzymes 1, inositol polyphosphate 5-phosphatase (I) 2, inositol polyphosphate 1-phosphatase 3,I(1,4,5)P3 3-kinase 4, inositol polyphosphate 4-phosphatase 5, inositol polyphosphate 3-phosphatase 6, inositol monophosphate phosphatase 7, I(1,3,4)P3 6-kinase/I(3,4,5,6)P4 1-kinase 8, Ipmk 9, DIPP 10, IP6 kinase 11, Ipk 1 12, MIPP 13, PP-IP5 kinase. 

IDPN [1,(1 i in i nod i p ropion it rile MIPP multiple inositol polyphosphate phosphatase... 

The Li+-induced inhibition of IMPase also results in increases in the levels of the other monophosphates, Ins(3)P, and Ins(4)P, although the increase is less than for Ins(l)P in the brain. Increases in the levels of the bisphosphates are also observed and these increases are believed to be related to the Li+-induced inhibition of another enzyme in this cycle, inositol polyphosphate 1-phosphatase [92], which dephosphorylates both Ins(l,3,4)P3 and Ins(l,4)P2, producing Ins(3,4)P2 and Ins(4)P, re-... 

Inositol Monophosphate Phosphatase and Inositol Polyphosphate 1 -Phosphatase... 

Figure 6. Schematic representation of inositol monophosphate phosphatase (left) and inositol polyphosphate 1-phosphatase (right), showing the helical (green cylinders) and (3-sheet (yellow arrows) regions. The monophosphatase is complexed with lns(1)P (solid spheres) and Gd3+ (orange sphere) in the binding cleft and the polyphosphatase has two Mg2+ (lilac spheres) ions. (The coordinates were obtained from the Brookhaven Protein Data Bank).

Fig. 13. Photoaffinity probes for studying transcription factors, inositol-polyphosphate binding proteins, and biopolymers containing an SH2 domain...

Arii T, Ohyanagi M, Shibuya J, Iwasaki T 1999 Increased function of the voltage-dependent calcium channels, without increase of Ca2+ release from the sarcoplasmic reticulum in the arterioles of spontaneous hypertensive rats. Am J Hypertens 12 1236-1242 Attree O, Olivos IM, Okabe I et al 1992 The Lowe s oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature 358 239-242 Brading AF, Turner WH 1994 The unstable bladder towards a common mechanism. Br J Urol 73 3-8... 

IPPc Inositol polyphosphate phosphatase, catalytic domain homologs E(MFP) 4(4) 5(5) ... 

Kimura T., Sakamoto, H., Appella, E., and Siraganian, R.P. 1997. The negative signaling molecule SH2 domain containing inositol polyphosphate 5-phosphatase (SHIP) binds to the tyrosine phosphorylated P subunit of the high affinity IgE receptor. J. Bio.Chem. 272 ... 

Lioubin, M.N., Algate, P.A., Tsai, S., Carlberg, K., Aebersold, R., and Rohrschneider, L.R., 1996, pl50 P, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity. Genes Dev. 10 1084-1095. 

Pesesse, X., Deleu, S., De Smedt, F., Drayer, L., Emeux, C., 1997, Identification of a second SH2-domain containing protein closely related to the phosphatidyl inositol polyphosphate 5-phosphatase SHIP. Biochem. Biophys. Res. Common. 239 697-700. 

Smith CL, Peterson CL (2005) A conserved Swi2/Snf2 ATPase motif couples ATP hydrolysis to chromatin remodeling. Mol Cell Biol 25 5880-5892 Steger DJ, Haswell ES, Miller AL, Wente SR, O Shea EK (2003) Regulation of chromatin remodeling by inositol polyphosphates. Science 299 114-116... 

Inositol-1,4,5-trisphosphate 5-phosphatase [EC 3.1.3.56], also known as inositol trisphosphate phosphomonoester-ase and inositol polyphosphate 5-phosphatase, catalyzes the hydrolysis of D-myo-inositol 1,4,5-trisphosphate to produce D-myo-inositol 1,4-bisphosphate and orthophosphate. The type I enzyme (but not the type II enzyme) will also hydrolyze inositol 1,3,4,5-tetrakisphosphate at the 5-position. However, neither of the two... 

Keywords Hsp90 IGF-IR Inositol polyphosphate mTor PDKl PI3K Phosphatidylinositol Phospholipids PKB... 

Kennedy ED, Challiss RJ, Nahorski SR Lithium reduces the accumulation of inositol polyphosphate second messengers following cholinergic stimulation of cerebral cortex slices. J Neurochem 53 1652-1655, 1989... 

Kennedy ED, Challiss RAJ, Ragan Cl, et al Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices. Biochem J 267 781-786, 1990... 

Inositol polyphosphate 1-phosphatase Another enzyme in inositol recycling inhibited by lithium, resulting in depletion of substrate for IP3 production (Figure 29-4)... 

---