9l0i

Structural highlights

Function

PLPP1_HUMAN Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P (PubMed:10962286, PubMed:17379599, PubMed:9305923, PubMed:9607309, PubMed:9705349). Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (PubMed:9607309). Through its extracellular phosphatase activity allows both the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (PubMed:10962286, PubMed:12909631, PubMed:15461590, PubMed:17379599). It is for instance essential for the extracellular hydrolysis of S1P and subsequent conversion into intracellular S1P (PubMed:17379599). Involved in the regulation of inflammation, platelets activation, cell proliferation and migration among other processes (PubMed:12909631, PubMed:15461590). May also have an intracellular activity to regulate phospholipid-mediated signaling pathways (By similarity).[UniProtKB:O08564]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Roberts RZ, Morris AJ. Role of phosphatidic acid phosphatase 2a in uptake of extracellular lipid phosphate mediators. Biochim Biophys Acta. 2000 Aug 24;1487(1):33-49. PMID:10962286 doi:10.1016/s1388-1981(00)00081-0
2. ↑ Smyth SS, Sciorra VA, Sigal YJ, Pamuklar Z, Wang Z, Xu Y, Prestwich GD, Morris AJ. Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity. J Biol Chem. 2003 Oct 31;278(44):43214-23. PMID:12909631 doi:10.1074/jbc.M306709200
3. ↑ Zhao Y, Usatyuk PV, Cummings R, Saatian B, He D, Watkins T, Morris A, Spannhake EW, Brindley DN, Natarajan V. Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium release, NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells. Biochem J. 2005 Jan 15;385(Pt 2):493-502. PMID:15461590 doi:10.1042/BJ20041160
4. ↑ Zhao Y, Kalari SK, Usatyuk PV, Gorshkova I, He D, Watkins T, Brindley DN, Sun C, Bittman R, Garcia JG, Berdyshev EV, Natarajan V. Intracellular generation of sphingosine 1-phosphate in human lung endothelial cells: role of lipid phosphate phosphatase-1 and sphingosine kinase 1. J Biol Chem. 2007 May 11;282(19):14165-77. PMID:17379599 doi:10.1074/jbc.M701279200
5. ↑ Kai M, Wada I, Imai Si, Sakane F, Kanoh H. Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase. J Biol Chem. 1997 Sep 26;272(39):24572-8. PMID:9305923 doi:10.1074/jbc.272.39.24572
6. ↑ Hooks SB, Ragan SP, Lynch KR. Identification of a novel human phosphatidic acid phosphatase type 2 isoform. FEBS Lett. 1998 May 8;427(2):188-92. PMID:9607309 doi:10.1016/s0014-5793(98)00421-9
7. ↑ Roberts R, Sciorra VA, Morris AJ. Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform. J Biol Chem. 1998 Aug 21;273(34):22059-67. PMID:9705349 doi:10.1074/jbc.273.34.22059