{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLPP1, also known as lipid phosphate phosphatase‐1 (LPP1), plays a key role in the regulation of extracellular lipid phosphates, acting to dephosphorylate bioactive lipids that modulate cellular behavior. In ovarian cancer cells, decreased LPP1 mRNA levels correlate with elevated lysophosphatidic acid (LPA) concentrations, and restoration of LPP1 activity enhances LPA hydrolysis. This enzymatic action is accompanied by reduced cell proliferation and colony formation as well as increased apoptosis, suggesting that LPP1 functions as an important negative regulator of tumorigenic signaling pathways through its control over LPA levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its catalytic activities, the subcellular localization of PLPP1 is critical for its function. Biochemical studies have demonstrated that PLPP1 is associated with distinct lipid raft microdomains. Although it is soluble in Triton X-100, PLPP1 remains insoluble in CHAPS and segregates into membrane regions separate from those occupied by the closely related isoform LPP3. This spatial partitioning within the plasma membrane likely fine-tunes its access to substrates and its interactions with other signaling molecules, thereby contributing to its non-redundant physiological roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, a splice variant of PLPP1, known as LPP1a, has been shown to exhibit the highest catalytic activity toward phosphorylated forms of immunomodulatory agents such as FTY720-P, a sphingosine 1-phosphate analog. Endothelial cells, which notably express significant levels of LPP1a, utilize this robust phosphatase activity to dephosphorylate FTY720-P in plasma. This function is pivotal for modulating sphingolipid signaling pathways that regulate T cell egress from lymphoid organs, underscoring PLPP1’s broad impact on immune modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Janos L Tanyi, Yutaka Hasegawa, Ruth Lapushin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14506139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14506139"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Masahiro Kai, Fumio Sakane, Yan-Jun Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lipid phosphate phosphatases 1 and 3 are localized in distinct lipid rafts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvj195"}], "href": "https://doi.org/10.1093/jb/mvj195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17005594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17005594"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masao Yamanaka, Yoshihiro Anada, Yasuyuki Igarashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A splicing isoform of LPP1, LPP1a, exhibits high phosphatase activity toward FTY720 phosphate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.07.165"}], "href": "https://doi.org/10.1016/j.bbrc.2008.07.165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18755152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18755152"}]}]}]}