Lipid 1-phosphatase activity

The classical PTPs can be subdivided into receptorlike PTPs and nonreceptor, cytosolic PTPs. The second category of PTPs are broadly defined as dual specificity phosphatases (DSPs), which dephosphorylate pSer/ pThr as well as pTyr. MAP kinase phosphatases (MKPs) ( MAP kinase cascades) and PTEN are examples of DSP family members. Remarkably, PTEN also has lipid phosphatase activity that is specific for phosphatidylinositol-3,4,5-trisphosphate generated in response to the actions of PI3K. Finally, the class of low molecular mass (LM-) PTPs and that of CDC25 PTPs accomplish the cells repertoire of PTPs (Fig. 3). 

The great importance of PtdIns(3,4,5)P3 metabolism for growth regulation is illustrated by the observation that an enzyme of PtdIns(3,4,5)P3 metabolism has been identified as a tumor suppressor protein (Wu et al., 1998). PTEN tumor suppressor protein has lipid phosphatase activity that is specific for hydrolysis of PtdIns(3,4,5)P3. It is assumed that PTEN lipid phosphatase is a negative regulator of the Akt pathway by lowering the concentration of PtdIns(3,4,5)P3 and counteracting stimulation of Akt kinase. 

Aleem E et al (2005) Cdc2-cyclin E complexes regulate the Gl/S phase transition. Nat Cell Biol 7 831-836 Alexandropoulos K et al (1995) Proline-rich sequences that bind to Src homology 3 domains with individual specificities. Proc Natl Acad Sci USA 92 3110-3114 Ali lU etal (1999) Mutational spectraof PTEN/MMACl gene a tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst 91 1922-1932... 

Lipid-free (Na+, K+)-ATPase is incapable of hydrolyzing ATP or p-nitrophenyl phosphate. The precise role of the lipid and the specificity for the lipid have not yet been determined. The addition of lipid to the delipidated enzyme brings about conformational changes, with phosphatase activity regenerated before ATPase activity.51 It seems evident that the lipid will affect the conformation of the enzyme and determine membrane fluidity, which is relevant to conformational change. 

Anandamide was discovered as a high-affinity ligand for CB receptors in 1992 (Devane et al., 1992). Anandamide is produced in response to an increase in intracellular Ca2+ levels or activation of G-protein-coupled receptors (e.g., D2 receptors) (Piomelli, 2003). In mammalian tissues, anandamide is present at concentrations of 1-50 pmol/g (Fig. 4), and can be formed through three distinct biochemical pathways (1) the direct hydrolysis of NAPE by a NAPE-specific phospholipase D (NAPE-PLD) (Okamoto et al., 2005 Wang et al., 2006) (2) the hydrolysis of lyso-NAPE or glycerophospho-anandamide by a specific PLD (Leung et al., 2006 Simon and Cravatt, 2008 Sun et al., 2004) and (3) the hydrolysis of phospho-anandamide by a lipid phosphatase (Liu et al., 2006, 2007) (Fig. 1). 

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... 

A novel DG pyrophosphate phosphatase has been identified in yeast (G.M. Carman, 1997). The enzyme has PA phosphatase activity but prefers DG pyrophosphate as substrate. A yeast mutant defective in the pyrophosphatase gene is viable and accumulates DG pyrophosphate (G.M. Carman, 1998). The enzyme is similar to the mammalian plasma membrane PA phosphatase that also hydrolyzes DG pyrophosphate. The biological function of DG pyrophosphate is unknown. Since this lipid is present at a very low level in yeast (0.18 mol% of total phospholipids), DG pyrophosphatase might have a signaling function. 

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