磷脂信号分子与激素分泌(2)
从人肝脏组织中克隆出人PA-PLA1基因(GenBank accession no.DQ315474)，该基因定位于14q22，mRNA长2923bp，编码一个由745个氨基酸残基组成的蛋白多肽。通过序列比对分析，发现该基因同哺乳动物中具有磷脂酶活性的P125蛋白和KIAA0725蛋白[17]存在一定的相似性。现普遍认为KIAA0725蛋白，P125蛋白及PA-PLA1是位于胞内的亲磷脂酸磷酸酶，但三种蛋白在细胞内定位及生理功能均有差别[18]。牛PA-PLA1位于细胞膜上，对膜上的磷脂酸有高度的催化活性[19]，并影响PLD或甘油激酶介导的信号传导通路[15]。P125蛋白定位于内质网上，其与CopⅡ包被成分Sec23P相互作用，参与将蛋白质从内质网运输到高尔基体[20]。最近，有研究指出KIAA0725蛋白位于高尔基体内并促进高乐尔基体分泌小泡的形成，但对布雷菲德菌素A诱导的高尔基转运小泡逆向转运无作用[21]。
鉴于PA-PLA1酶活性影响细胞内PA和LPA信号水平，笔者推测PA-PLA1可能参与了PA和LPA依赖性细胞转运小泡的形成以及高尔基体的组装等细胞物质运输过程。
, http://www.100md.com
4结语与展望
总之，PA和LPA作为脂质代谢的重要中间产物,其在激素分泌中的作用是复杂的。然而PA 及LPA水平又受到PA-PLA1、PLD、PLC等酶活性的调节，已有研究证实PLD、PLC参与了内分泌细胞的分泌功能，但目前对于人PA-PLA1具体的生理功能的研究仍处于空白，PA-PLA1是否涉及内分泌细胞激素分泌的信号转导过程仍不明了，还需要进一步深入探讨。同时在激素分泌信号转导过程中，PLA、PLD及PLC各自扮演何种角色，也将是今后研究的重要内容。
参考文献
[1]Reeves HL,Thompson MG,Dack GL,et al.The role of phosphatidic acid in platelet-derived growth factor induced proliferation of rat hepatic stellate cells.Hepatology,2000,31095-31100.
, 百拇医药
[2]Regier DS,Greene DAG,Sergeant S,et al.Phosphorylation of P22phox is mediated by phospholipase D-dependent and -independent mechanisms.J Biol Chem,2000,275：28406-28412.
[3]Schmidt A,Wolde M,Thiele C,Fest W，et al.Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.Nature,1999,401(6749):133-141.
[4]Weigert R.Silletta MG,Spano S,et al.CtBp/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid.Nature,1999,402(6760):429-433.
, 百拇医药
[5]Van Leeuwen FN,Giepmans BN.Lysophosphatidic acid:mitogen and motility factor.Biochem Soc Trans,2003,31(Pt 6):1209-1212.
[6]Kostenis E.Novel Clusters of Receptors for Sphingosine-1-phosphate,Sphingosylphosphorylcholine,and (Lyso)-phosphatidic Acid :New Receptor for “old”Ligands.Journal of Cellular Biochemistry,2004,92(5):923-936.
[7]T Soga,T Ohishi,T Matsui,T Saito,et al.Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor.Biochem Biophys Res Commun,2005,326(4):744-51.
, 百拇医药
[8]K Yea,J Kim,S Lim,et al.Lysophosphatidic acid regulates blood glucose by stimulating myotube and adipocyte glucose uptake.J Mol Med,2008,86(2):211-220.
[9]Siddhanta A,Backer JM,Shields D.Inhibition of phosphatidic acid synthesis alters the structure of the Golgi apparatus and inhibits secretion in endocrine cells.J Biol Chem,2000,275:12023-12031.
[10]Sophia Thore,Oleg Dyachok,Erik Gylfe,et al.Feedback activation ofphospholipase C via intracellular mobilization and store-operated influx of Ca2+ in nsulin-secreting -cells.Cell Science,2005：4463-4471.
, 百拇医药
[11]郑宏庭，李丙蓉，方芳,等.葡萄糖对βHC9细胞内磷脂酶C及钙离子浓度的影响.第三军医大学学报,2007,29(3).
[12]周恒宇，邓华聪,郑宏庭,等.磷脂酶Cβ1过表达对葡萄糖刺激胰岛素分泌的影响.第三军医大学学报,2009,31(19).
[13]Lennart Asp,Fredrik Kartberg,Julia Fernandez-Rodriguez,et al.Early Stages of Golgi Vesicle and Tubule Formation Require Diacylglycerol.Mol Biol Cell,2009,20:780-790.
[14]Higgs HN,Glomset JA.Purification and properties of a phosphatidic acid-preferring phospholipase A1 from bovine brain testis.Examination of the molecular basis of its actication.J Biol Chem,1996，271(18):10874-10883., 百拇医药(于婕 曾思恩 刘永明)
鉴于PA-PLA1酶活性影响细胞内PA和LPA信号水平，笔者推测PA-PLA1可能参与了PA和LPA依赖性细胞转运小泡的形成以及高尔基体的组装等细胞物质运输过程。
, http://www.100md.com
4结语与展望
总之，PA和LPA作为脂质代谢的重要中间产物,其在激素分泌中的作用是复杂的。然而PA 及LPA水平又受到PA-PLA1、PLD、PLC等酶活性的调节，已有研究证实PLD、PLC参与了内分泌细胞的分泌功能，但目前对于人PA-PLA1具体的生理功能的研究仍处于空白，PA-PLA1是否涉及内分泌细胞激素分泌的信号转导过程仍不明了，还需要进一步深入探讨。同时在激素分泌信号转导过程中，PLA、PLD及PLC各自扮演何种角色，也将是今后研究的重要内容。
参考文献
[1]Reeves HL,Thompson MG,Dack GL,et al.The role of phosphatidic acid in platelet-derived growth factor induced proliferation of rat hepatic stellate cells.Hepatology,2000,31095-31100.
, 百拇医药
[2]Regier DS,Greene DAG,Sergeant S,et al.Phosphorylation of P22phox is mediated by phospholipase D-dependent and -independent mechanisms.J Biol Chem,2000,275：28406-28412.
[3]Schmidt A,Wolde M,Thiele C,Fest W，et al.Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.Nature,1999,401(6749):133-141.
[4]Weigert R.Silletta MG,Spano S,et al.CtBp/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid.Nature,1999,402(6760):429-433.
, 百拇医药
[5]Van Leeuwen FN,Giepmans BN.Lysophosphatidic acid:mitogen and motility factor.Biochem Soc Trans,2003,31(Pt 6):1209-1212.
[6]Kostenis E.Novel Clusters of Receptors for Sphingosine-1-phosphate,Sphingosylphosphorylcholine,and (Lyso)-phosphatidic Acid :New Receptor for “old”Ligands.Journal of Cellular Biochemistry,2004,92(5):923-936.
[7]T Soga,T Ohishi,T Matsui,T Saito,et al.Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor.Biochem Biophys Res Commun,2005,326(4):744-51.
, 百拇医药
[8]K Yea,J Kim,S Lim,et al.Lysophosphatidic acid regulates blood glucose by stimulating myotube and adipocyte glucose uptake.J Mol Med,2008,86(2):211-220.
[9]Siddhanta A,Backer JM,Shields D.Inhibition of phosphatidic acid synthesis alters the structure of the Golgi apparatus and inhibits secretion in endocrine cells.J Biol Chem,2000,275:12023-12031.
[10]Sophia Thore,Oleg Dyachok,Erik Gylfe,et al.Feedback activation ofphospholipase C via intracellular mobilization and store-operated influx of Ca2+ in nsulin-secreting -cells.Cell Science,2005：4463-4471.
, 百拇医药
[11]郑宏庭，李丙蓉，方芳,等.葡萄糖对βHC9细胞内磷脂酶C及钙离子浓度的影响.第三军医大学学报,2007,29(3).
[12]周恒宇，邓华聪,郑宏庭,等.磷脂酶Cβ1过表达对葡萄糖刺激胰岛素分泌的影响.第三军医大学学报,2009,31(19).
[13]Lennart Asp,Fredrik Kartberg,Julia Fernandez-Rodriguez,et al.Early Stages of Golgi Vesicle and Tubule Formation Require Diacylglycerol.Mol Biol Cell,2009,20:780-790.
[14]Higgs HN,Glomset JA.Purification and properties of a phosphatidic acid-preferring phospholipase A1 from bovine brain testis.Examination of the molecular basis of its actication.J Biol Chem,1996，271(18):10874-10883., 百拇医药(于婕 曾思恩 刘永明)