Phosphatases lipid phosphate

A murine SIP phosphatase gene, which encodes a 430 amino acid (47.7kDa) protein, has recently been cloned (Mandala et al, 2000). This enzyme bears similarity to a family of lipid phosphate phosphatases (LPPs) (Brindley and Waggoner, 1998) in that it has invariant residues within the three domains of the common predicted catalytic site ((K-X6-RP)-Xu.37-(S-X-H)-X4o.46-(R-Xs-H-X3-D)) although the spacing between the domains differs from the LPPs. In contrast to LPPs, SIP phosphatase is highly... 

Sphingosine phosphate phosphatases (Sgppl, Sgpp2) Lipid phosphate phosphatases (Ppap2a, Ppap2b)... 

Aldeiton, F.A, Darroch, P.I., Sambi, B., McKie, A., Pyne, N.J. and Pyne, S., 2001, G-protein-coupled receptor signaling to p42/p44 mitogen-activated protein kinase is attenuated by lipid phosphate phosphatases 1,1a and 2 in HEK 293 cells,./. Biol. Chem. 276 13452-13460. 

Smyth SS, Sciorra VA, Sigal YJ, Pamuklar Z, Wang Z, Xu Y, Prestwich GD, Morris AJ (2003) Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaUng in platelets studies using chemical inhibitors of lipid phosphate phosphatase activity. J Biol Chem 278 43214 3223... 

Finally, dephosphorylation of LPA to monoacylglycerol by lipid phosphate phosphatases can occur. 

Nevertheless, interest in the lipid phosphate phosphatases continues to flourish, not least because of their therapeutic potential. For example, lipid phosphate phosphatase activity is reduced in ra -transformed cells (Martin et al., 1993), regulates adipose tissue development (Simon et al., 2002) and reduces the growth and survival of ovarian cancer cells, which may provide a novel strategy for the treatment of this and other cancers (Tanyi et al., 2003). A parallel may be drawn here with PAF acetylhydrolase, which inactivates PAF. Indeed, the recombinant form of this enzyme has been used to reduce oedema and vascular leakage in addition to inflammation in enterocolitis, pancreatitis and diabetes (Prescott et al., 2000). 

Hooks, SB, Santos, WL, Im, DS, Heise, CE, Macdonald, TL and Lynch, KR (2001) Lysophosphatidic acid-induced mitogenesis is regulated by lipid phosphate phosphatases and is Edg-receptor dependent. 7 BZnZ Chem, 276,4611-4621. 

Xu, J, Love, LM, Singh, L Zhang, Q-X, Dewald, J, Wang, D-A, Fischer, DJ, Tigyi, G, Berthiaume, LG, Waggoner, DW and Brindley, DN (2000) Lipid phosphate phosphatase-1 and Ca2+ control lysophosphatidate signalling through EDG-2 receptors. JBiol Chem, 275, 27520-27530. 

Zhang, QX, Pilquil, CS, Dewald, J, Berthiaume, LG and Brindley, DN (2000) Identification of structurally important domains of lipid phosphate phosphatase-1 implications for its sites of action. Biochem J, 345, 181-184. 

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