Pilquil C, Ling Z C, Singh I, Buri K, Zhang Q X, Brindley D N
Department of Biochemistry, Signal Transduction Research Group, 357 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada, T6G 2S2.
Biochem Soc Trans. 2001 Nov;29(Pt 6):825-30. doi: 10.1042/0300-5127:0290825.
The serum-derived lipid growth factors, lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P), activate cells selectively through different members of a family of endothelial differentiation gene (EDG) receptors. Activation of EDG receptors by LPA and S1P provides a variety of signalling cascades depending upon the G-protein coupling of the different EDG receptors. This leads to chemotactic and mitogenic responses, which are important in wound healing. For example, LPA stimulates fibroblast division and S1P stimulates the chemotaxis and division of endothelial cells leading to angiogenesis. Counteracting these effects of LPA and S1P, are the actions of lipid phosphate phosphatases (LPP, or phosphatidate phosphohydrolases, Type 2). The isoform LPP-1 is expressed in the plasma membrane with its active site outside the cell. This enzyme is responsible for 'ecto-phosphatase' activity leading to the degradation of exogenous lipid phosphate mediators, particularly LPA. Expression of LPP-1 decreases cell activation by exogenous LPA. The mechanism for this is controversial and several mechanisms have been proposed. Evidence will be presented that the LPPs cross-talk with EDG and other growth factor receptors, thus, regulating the responses of the cells to lipid phosphate mediators of signal transduction.
血清衍生的脂质生长因子溶血磷脂酸（LPA）和1-磷酸鞘氨醇（S1P），通过内皮分化基因（EDG）受体家族的不同成员选择性地激活细胞。LPA和S1P对EDG受体的激活取决于不同EDG受体的G蛋白偶联，从而提供多种信号级联反应。这会导致趋化和有丝分裂反应，这些反应在伤口愈合中很重要。例如，LPA刺激成纤维细胞分裂，S1P刺激内皮细胞的趋化和分裂，从而导致血管生成。脂质磷酸磷酸酶（LPP，或2型磷脂酸磷酸水解酶）的作用与LPA和S1P的这些作用相反。同工型LPP-1在质膜中表达，其活性位点在细胞外。这种酶负责“胞外磷酸酶”活性，导致外源性脂质磷酸介质，特别是LPA的降解。LPP-1的表达降低了外源性LPA对细胞的激活作用。其机制存在争议，已经提出了几种机制。将提供证据表明LPP与EDG和其他生长因子受体相互作用，从而调节细胞对脂质磷酸信号转导介质的反应。
