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研究生:姜宏哲
研究生(外文):Jiang-Hung Je
論文名稱:探討LPA藉由p42/p44MAPK和Akt訊息傳遞路徑引發氣管平滑肌之增生
論文名稱(外文):Lysophosphatidic Acid-induced CellProliferation via p42/p44 MAPK and Akt Pathways in Tracheal Smooth Muscle Cells
指導教授:楊春茂楊春茂引用關係
指導教授(外文):Chuen-Mao Yang
學位類別:碩士
校院名稱:長庚大學
系所名稱:天然藥物研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:103
中文關鍵詞:氣管平滑肌之增生
外文關鍵詞:Lysophosphatidic AcidLPAproliferationCT
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LPA 為具有生物活性的磷脂質,可以調控細胞的許多生理功能,像是增生。然而,由 LPA 引發氣管平滑肌細胞增生的反應機構並不是很清楚,而我們的研究發現 LPA 會藉由 mitogen-activated protein kinases (MAPKs) 和 Akt 訊號傳遞路徑引發氣管平滑肌細胞的增生。 U0126 為 MEK1/2 的抑制劑、 AG1478 為 EGFR 的抑制劑、 AG1296 為 PDGFR 的抑制劑、 wortmannin 為 PI3K 的抑制劑、 BAPTA 為 Ca2+ 的螯合劑,他們皆會抑制 LPA 引發細胞的增生。不僅如此 U0126, LY294002 , 或是 wortmannin 也都確實會去減弱 LPA 所引發 p42/p44 MAPK 和 Akt 的磷酸化,經由以上的這些結果我們得知LPA 需要藉由活化 p42/p44 MAPK 和 Akt 訊號傳遞路徑引發氣管平滑肌細胞的增生,了解 LPA 引發氣管平滑肌細胞細胞增生的反應機構,或許可以提供治療呼吸道疾病一個有潛力的價值。
Lysophosphatidic acid (LPA) is one of bioactive phospholipids which play a regulatory role in a wide range of physiological functions such as proliferation. However, the mechanisms underlying LPA-induced cell proliferation in tracheal smooth muscle cells (TSMC) remain unclear. We report that the mitogen-activated protein kinases (MAPKs) and Akt pathways participated in cell proliferation induced by LPA in TSMC. LPA increased cell proliferation, which was attenuated by inhibitors of MEK1/2 (U0126), EGFR (AG1478), PDGFR (AG1296), PI3K (wortmannin), and Ca2+ chelator (BAPTA). Accordingly, LPA induced phosphorylation of p42/p44 MAPK and Akt which was attenuated by U0126, LY294002, or wortmannin, respectively. These results suggest that in TSMC, activation of p42/p44 MAPK and Akt pathways is essential for LPA-induced cell proliferation. Understanding the mecahnisms involved in LPA-induced cell proliferation on TSMC may provide potential therapeutic values in the treatment of airway diseases.
目 錄 (Contents)
頁 (Page)
目錄 (Contents)……………………………………………………….....I
縮寫表 (Abbreviations)………………………………………………...III
抑制劑作用……………………………………………………….…….VII
英文摘要 (Abstract in English)…………………………………………1
中文摘要 (Abstract in Chinese)………………………………………...2
緒論 (Introduction)………………………………………………….. …3
附圖及附表……………………………………………………………..25
材料與方法 (Materials and Methods)……………………………........38
實驗結果 (Experimental Results)………………………....………..….44
1. CTSMCs 表現大量 LPA1 與 LPA3 receptor 之 mRNA
2. LPA 引起 CTSMCs 內 p42/p44 MAPK 及 Akt 的活化並誘發細胞的增生
3. LPA 經由 PTX-sensitive Gi-protein誘發 Akt 及p42/p44 MAPK 的活化且刺激 DNA 合成
4. LPA 經由 Src 誘發 Akt 及 p42/p44 MAPK 的活化且刺激 DNA合成
5. PC-PLC PI-PLC 對於 LPA 引起 p42/p44 MAPK 磷酸化且刺激 DNA 合成的影響
6. LPA 是否經由 Ca2+ 誘發 Akt 及 p42/p44 MAPK 的活化且刺激DNA 合成
7. LPA 是否經由 PKC 誘發 Akt 及 p42/p44 MAPK 的活化且刺激DNA 合成
8. LPA 是否經由 EGFR轉活化(Transactivation)來誘發 Akt 及 p42/p44 MAPK 的活化且刺激 DNA 合成
9. LPA 是否經由 PI3K 誘發 Akt 及 p42/p44 MAPK 的活化且刺激DNA 合成
10. MEK 抑制劑對於 LPA引起 p42/p44 MAPK 磷酸化且刺激 DNA合成的響
討論 (Discussion)……………………………………………………..50
數據 (Data)…………………………………………………………….55
參考文獻 (References)…………………………………………….......89
Ahn S, Maudsley S, Luttrell LM, Lefkowitz RJ and Daaka Y. (1999) Src-mediated Tyrosine Phosphorylation of Dynamin Is Required for 2-Adrenergic Receptor Internalization and Mitogen-activated Protein Kinase Signaling. J. Biol. Chem. 274, 1185-1188.
Alderton F, Rakhit S, Kong KC, Palmer T, Sambi B, Pyne S and Pyne NJ. (2001) Tethering of the platelet-derived growth factor receptor to G protein-coupled receptors. NOVEL PLATFORM FOR INTEGRATIVE SIGNALING BY THESE RECEPTOR CLASSES IN MAMMALIAN CELLS. J. Biol. Chem. 276, 28578-28585.
Alessi DR, Caudwell FB, Andjelkovic M, Hemmings BA and Cohen P. (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15, 6541-6551.
Alessi DR, James SR, Downes CP, Holmes AB, Gaåney PR, Reese CB and Cohen P. (1997) Characterization of a 3-phosphoinositide -dependent protein kinase which phosphorylates and activates protein kinase B. Curr. Biol. 7, 261-269.
An S, Bleu T, Hallmark OG and Goetzl EJ. (1998) Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J Biol Chem 273, 7906-7910.
Anderson KE, Coadwell J, Stephens LR and Hawkins PT. (1998) Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B. Curr. Biol. 8, 684-691.
Andjelkovic M, Alessi DR, Meier R, Fernandez A, Lamb NJ, Frech M, Cron P, Cohen P, Lucocq JM and Hemmings BA. (1997) Role of translocation in the activation and function of protein kinase B. J. Biol. Chem. 272, 31515-31524.


Armour CL, Diment LM and Black JL. (1998) Relationship between smooth muscle volume and contractile response in airway tissue. Isometric versus isotonic measurement. J. Pharmacol. 245, 687-691.
Asano T, Kanda A, Katagiri H, Nawano M, Ogihara T, Inukai K, Anai M, Fukushima Y, Yazaki Y, Kikuchi M, Hooshmand-Rad R, Heldin CH, Oka Y and Funaki M. (2000) p110beta is upregulated during differentiation of 3T3-L1 cells and contributes to the highly insulinresponsive glucose transport activity. J. Biol. Chem. 275, 17671-17676.
Balciunaite E, Jones S, Toker A and Kazlauskas A (2000) PDGF initiates two distinct phases of protein kinase C activity that make unequal contributions to the G0 to S transition. Curr. Biol. 10, 261-267.
Billah MM, Lapetina EG and Cuatrecasas P. (1981) Phospholipase A2 activity specific for phosphatidic acid. A possible mechanism for the production of arachidonic acid in platelets. J. Biol. Chem. 256, 399-5403.
Biwa T, Sakai M, Matsumura T, Kobori S, Kaneko K, Miyazaki A, Hakamata H, Horiuchi S and Shichiri M. (2000) Sites of action of protein kinase C and phosphatidylinositol 3-kinase are distinct in oxidized low density lipoprotein-induced macrophage proliferation. J. Biol. Chem. 275, 5810-5816.
Brennan P, Mehl AM, Jones M and Rowe M (2002) Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells. Oncogene, 21, 1263-1271.
Brown RA, Domin J, Arcaro A, Waterfield MD and Shepherd PR. (1999) Insulin activates the alpha isoform of class II phosphoinositide 3-kinase. J. Biol. Chem. 274, 14529-14532.
Burgering BM and Coffer PJ. (1995) Potein kinase B(c-Akt) in phophatidylinositol-3-OH kinase signal transduction. Nature, 376, 599-602.


Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96, 857-868.
Brunet A, Park J, Tran H, Hu LS, Hemmings BA and Greenberg ME. (2001) Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol. Cell. Biol. 21, 952-965.
Castagliuolo I, Valenick L, Liu J and Pothoulakis C. (2000) Epidermal growth factor receptor transactivation mediates substance P-induced mitogenic responses in U-373 MG cells. J. Biol. Chem. 275, 26545-26550.
Chen R, Kim O, Yang J, Sato K, Eisenmann KM, McCarthy J, Chen H and Qiu Y. (2001) Regulation of Akt/PKB Activation by Tyrosine Phosphorylation. J. Biol. Chem. 276, 31858-31862.
Chen CC, Wang JK, Chen WC and Lin SB. (1998). Protein kinase C mediates lipopolysaccharide-induced nitric oxide synthase expression in primary astrocytes. J. Biol. Chem. 273, 19424-19430.
Chen YH, Pouyssegur J, Courtneidge SA and Obberghen-Schilling EV. (1994) Activation of Src family kinase activity by the G protein-coupled thrombin receptor in growth-responsive fibroblasts. J. Biol. Chem. 269, 27372-27377.
Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN and Testa JR. (1992) AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc. Natl. Acad. Scie. USA. 89, 9267-9271.
Chou MM, Hou W, Johnson J, Graham LK, Lee MH, Chen CS, Newton AC, Schaffhausen BS and Toker A. (1998) Regulation of protein kinase C ζ by PI 3-kinase and PDK-1. Curr. Biol. 8, 1069-1077.

Choudhury GG, Karamitsos C, Hernandez J, Gentilini A, Bardgette J and Abboud HE. (1997) PI-3-kinase and MAPK regulate mesangial cell proliferation and migration in response to PDGF. Am. J. Physiol. 273, F931-F938.
Choudhury GG, Sylvia VL, Wang LM, Pierce J and Sakaguchi AY. (1991). The kinase insert domain of colony stimulating factor-1 receptor is dispenable for CSF-1 induced phosphatidylcholine hydrolysis. FEBS Lett. 282, 351-354.
Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S and Tigyi G. (2002) International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature. Pharmacol Rev. 54, 265-269.
Cobb MH. and Goldsmith EJ. (1995) How MAP kinases are regulated. J. Biol. Chem. 270, 14843-14846.
Cobb MH. (1999) MAP kinase pathways. Prog. Biophys. Mol. Biol. 71, 479-500.
Coffer PJ and Woodgett JR. (1991) Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP dependent and protein kinase C families. Eur. J. Biochem. 201, 475-481.
Cook SJ, Aziz N and McMahon M. (1999) The repertoire of fos and jun proteins expressed during the G1 phase of the cell cycle is determined by the duration of mitogen-activated protein kinase activation. Mol. Cell. Biol. 19, 330–341.
Craddock BL, Hobbs J, Edmead CE and Welham MJ. (2001) Phosphoinositide 3-kinase-dependent regulation of interleukin-3 -induced proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2. J. Biol. Chem. 276, 24274-83.
Cross DA, Alessi DR, Cohen P, Andjelkovich M and Hemmings BA. (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature, 378, 785-789.
Datta K, Bellacosa A, Chan TO and Tsichlis PN. (1996) Akt is a direct target of the Phosphatidylinositol 3-Kinase. J. Biol. Chem. 271, 30835-30839.
Daub H, Weiss FU, Wallasch C and Ullrich A. (1996) Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature, 379, 557-60.
Dayanir V, Meyer RD, Lashkari K and Rahimi N. (2001) Identification of tyrosine residues in vascular endothelial growth factor receptor-2/FLK-1 involved in activation of phosphatidylinositol 3-kinase and cell proliferation. J. Biol. Chem. 276, 17686-17692.
Denhardt DT. (1996) Signal-transducing protein phosphorylation cascades mediated by ras/rho proteins in the mammalian cell: the potential for multiplex signalling. Biochem. J. 318, 729-747.
Deprez J, Vertommen D, Alessi DR, Hue L and Rider MH. (1997) Phosphorylation and activation of heart 6-phosphofructo -2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J. Biol. Chem. 272, 17269-17275.
Didichenko SA, Tilton B, Hemmings BA, Ballmer-Hofer K and Thelen M. (1996) Constitutive activation of protein kinase B and phosphorylation of p47phox by a membrane-targeted phosphoinositide 3-kinase. Curr. Biol. 6, 1271-1278.
Dikic I, Tokiwa G, Lev S, Courtneidge SA and Schlessinger J. (1996) A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation. Nature, 383, 547-550.
Dimmeler S, Assmus B, Hermann C, Haendeler J and Zeiher AM. (1998) Fluid shear stress stimulates phosphorylation of Akt in human endothelial cells: involvement in suppression of apoptosis. Circ. Res. 83, 334-341.
Downward J. (1998) Ras signalling and apoptosis. Curr. Opin. Genet. Dev. 8, 49-54.
Duckworth BC, and Cantley LC. (1997) Conditional inhibition of the mitogen-activated protein kinase cascade by wortmannin: Dependence on signal strength. J. Biol. Chem. 272, 27665-27670.

Dutil EM, Toker A and Newton AC. (1998) Regulation of conventional protein kinase C isozymes by phosphoinositide- dependent kinase 1 (PDK-1). Curr. Biol. 8, 1366-1375.
Eguchi S, Dempsey PJ, Frank GD, Motley ED and Inagami T. (2001) Activation of MAPKs by Angiotensin II in Vascular Smooth Muscle Cells. Metalloprotease -dependent EGF receptor activation is required for activation of ERK and p38 MAPK but not for JNK. J. Biol. Chem. 276, 7957-7962.
Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomiya H, Motley ED, Kawakatsu H, Owada KM, Hirata Y, Marumo F and Inagami TJ. (1998) Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J. Biol. Chem. 273, 8890-8896.
Eichholtz T, Jalink K, Fahrenfort I and Moolenaar WH. (1993) Thre bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem. J. 291, 677-680.
Erickson JR, Wu JJ, Goddard JG, Tigyi G, Kawanishi K, Tomei LD and Kiefer MC. (1998) Edg-2/Vzg-1 couples to the yeast pheromone response pathway selectively in response to lysophosphatidic acid. J. Biol. Chem. 273, 1506-1510.
Exton JH. (1994) Phosphatidylcholine breakdown and signal transduction. Biochem. Biophys. Acta. 1212, 26-42.
Filippa N, SabelLe CL, HemmMings BA and Obberghen EV. (2000) Effect of Phosphoinositide-Dependent Kinase 1 on Protein Kinase B Translocation and Its Subsequent Activation. Mol. Cell. Biol. 20, 5712-5721.
Flynn P, Mellor H and Parker PJ. (2000) Rho-GTPase control of PRK activation by PDK1. J. Biol. Chem. 275, 11064-11070.

Franke TF, Yang SI, Chan TO, Datta K, Kazlauskas A, Morrison DK, Kaplan DR and Tsichlis PN. (1995) The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell, 81, 727-736.
Frech M, Andjelkovic M, Ingley E, Reddy KK, Falck JR and Hemmings BA. (1997) High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272, 8474-8481.
Freedman NJ, Kim LK, Murray JP, Exum ST, Brian L, Wu JH and Peppel K. (2002) Phosphorylation of the platelet-derived growth factor receptor-ß and epidermal growth factor receptor by G protein-coupled receptor kinase-2 mechanisms for selectivity of desensitization. J Biol Chem. 277, 48261-48269.
Fruman DA, Cantley LC and Carpenter CL. (1996) Structural organization and alternative splicing of the murine phosphoinositide 3-kinase p85 alpha gene. Genomics, 37, 113-21.
Fukushima N, Ishii I, Contos JJA, Weiner JA and Chun J. (2001) Lysophospholipid Receptors. Ann. Rev. Pharmacol. Toxicol. 41, 507-534.
Giehl K, Skripczynski B, Mansard A, Menke A and Gierschik P. (2000) Growth factor-dependent activation of the Ras-Raf-MEK-MAPK pathway in the human pancreatic carcinoma cell line PANC-1 carrying activated K-ras: implications for cell proliferation and cell migration. Oncogene, 19, 2930-42.
Gille H and Downward J. (1999) Multiple ras effector pathways contribute to G (1) cell cycle progression. J. Biol. Chem. 274, 22033-22040.
Goetzl EJ, Kong Y and Kenney JS. (1999) Lysophospholipid enhancement of human T cell sensitivity to diphtheria toxin by increased expression of heparin-binding epidermal growth factor. Proc. Assoc. Am. Physicians. 111(3), 259-269.


Gohla A, Harhammer R and Schultz G. (1998) The G-protein G13 but not G12 mediates signaling from lysophosphatidic acid receptor via epidermal growth factor receptor to Rho. J. Biol. Chem. 273, 4653-4659.
Gould GW, Jess TJ, Andrews GC, Herbst JJ, Plevin RJ and Gibbs EM. (1994) Evidence for a role of phosphatidylinositol 3-kinase in the regulation of glucose transport in Xenopus oocytes. J. Biol. Chem. 269, 26622-26625.
Harlan JE, Yoon HS, Hajduk PJ and Fesik SW. (1994) Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature, 371, 168-170.
Harlan JE, Yoon HS, Hajduk PJ and Fesik SW. (1995) Structural characterization of the interaction between a pleckstrin homology domain and phosphatidylinositol 4,5-bisphosphate. Biochem. 34, 9859-9864.
Haslam RJ, Koide HB and Hemmings BA. (1993) Pleckstrin domain homology. Nature, 363, 309-310.
Hecht JH, Weiner JA, Post SR and Chun J. (1996) Ventricular zone gene -1 (Vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J. Cell Biol. 135, 1071-1083.
Hershenson MB, Aghili S, Punjabi N, Hernandez C, Ray DW, Garland A, Glagov S and Solway J. (1992) Hyperoxia-induced airway hyperresponsiveness and remodeling in immature rats. Am. J. Physiol. 262, L26326-26329.
Hill CS and Treisman R. (1995) Differential activation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. EMBO J. 14, 5037– 5047.
Hubbard SR and Till JH. (2000). Protein tyrosine kinase structure and function. Annu. Rev. Biochem. 69, 373-398.


Ishii I, Contos JJ, Fukushima N and Chun J (2000) Functional comparisons of the lysophosphatidic acid receptors, LPA1/VZG-1/EDG-2, LPA2/EDG-4 and LPA3/ EDG-7 in neuronal cell lines using a retrovirus expression system. Mol Pharmacol. 58, 895-902.
James SR, Smith S, Paterson A, Harden TK and Downes CP. (1996) Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3, 4, 5-trisphosphate without subsequent activation. Biochem. J. 315, 709-713.
Katso R, Okkenhaug K, Ahmadi K, White S, Timms JD and Waterfield M. (2001) Cellular function of phosphoinositide 3-kinases: Implications for Development, Immunity, Homeostasis, and Cancer. Annu. Rev. Cell Dev. Biol. 17, 615-675.
Klemke RL, Yebra M, Bayna EM and Cheresh DA. (1994) Receptor tyrosine kinase signaling required for integrin alpha v beta 5-directed cell motility but not adhesion on vitronectin. J. Cell Biol. 127, 859-866.
Klippel A, Reinhard C, Kavanaugh WM, Apell G, Escobedo MA and Williams LT. (1996) Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways. Mol. Cell. Biol. 16, 4117-4127.
Kranenburg O, Moolenaar WH. (2001) Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled receptor agonists. Oncogene, 20, 1540-1546.
Kranenburg O, Poland M, van Horck FP, Drechsel D, Hall A and Moolenaar WH. (1999) Activation of RhoA by lysophosphatidic acid and Galpha12/13 subunits in neuronal cells: induction of neurite retraction. Mol. Biol. Cell. 10, 1851-1857.
Krugmann S, Hawkins PT, Pryer N and Braselmann S. (1999) Characterizing the interactions between the two subunits of the p101/p110gamma phosphoinositide 3-kinase and their role in the activation of this enzyme by G beta gamma subunits. J. Biol. Chem. 274, 17152-17158.
Lazaar AL and Panettieri RA Jr. (2003) Is airway remodeling clinically relevant in asthma? Am. J. Med. 115, 652-659.
Liu MK, Velit PH, Brownsey RW and Reiner NE. (1994). CD14-dependent activation of protein kinase C and mitogen-activated protein kinase (p42 and p44) in human monocytes treated with baterial lipopolysaccharide. J. Immunol. 153, 2642-2652.
Luquain C, Sciorra VA and Morris AJ. (2003) Lysophosphatidic acid signaling: how a small lipid does big things. Trends Biochem. Sci. 28, 377-383.
Marques SA, Dy LC, Southall M D, Yi Q, Smietana E, Kapur R, Marques M, Travers JB and Spandau DF. (2002) The platelet-activating factor receptor activates the extracellar signal-regulated kinase mitogen-activated protein kinase and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway. J. Pharmacol. Exp. 300, 1026-1035.
May MJ and Ghosh S. (1997) Rel/ NF-kB and IkB proteins: An overview. Semin. Cancer Biol. 8, 63-73.
Mayer BJ, Ren R, Clark KL and Baltimore D. (1993) A putative modular domain present in diverse signaling proteins. Cell, 73, 629-630.
Mclnnes C and Sykes BD. (1997). Growth factor receptor: structure, mechanism, and drug discovery. Biopolymers, 43, 339-366.
Mercurio F and Manning AM. (1999) Multiple signals converging on NF-κB. Curr. Biol. 11, 226-232.
Moolenaar WH. (1999) Bioactive Lysophospholipids and Their G Protein-Coupled Receptors. Exp. Cell Res. 253, 230-238.
Nishizuka Y. (1992). Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science, 258, 607-614.
Nishizuka Y. (1995). Protein kinase C and lipid singaling for and lipid signaling for sustained cellular response. FASEB J. 9, 484-496.


Panettieri RA, Murray RK, DePalo LR, Yadvish PA and Kotlikoff MI. (1989) A human airway smooth muscle cell line that retains physiological responsiveness. Am. J. Physiol. 256, 329-335.
Pare PD, Wiggs BR, James A, Hogg JC and Bosken C. (1991) The comparative mechanics and morphology of airways in asthma and in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 143, 1189-1193.
Parinandi NL, Roy S, Shi S, Cummings RJ, Morris AJ, Garcia JG and Natarajan V. (2001) Role of Src kinase in diperoxovanadate-mediated activation of phospholipase D in endothelial cells. Arch. Biochem. Biophys. 396(2), 231-343.
Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C, and Ullrich A. (1999). EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature, 402, 884-888.
Prpic V, Wciel JE, Somers SD, Diguiseppi J, Gomas SL, Pizzo SV, Hamilton TA, Herman B and Adams D. (1987). Effect of bacterial lipopolysaccharide on the hydrolysis of phosphatidylinositol-4,5-bisphophate in murine peritoneal macrophages. J. Immunol. 139, 526-533.
Qui MS and Green SH. (1992) PC12 cell neuronal differentiation is associated with prolonged p21ras activity and consequent prolonged ERK activity. Neuron. 9, 705-717.
Ribinson DR, Wu YM and Lin SF. (2000). The protein tyrosine kinase family of human genome. Oncogene, 19, 5548-5557.
Ridley AJ and Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell, 70, 389-399.
Robinson MJ and Cobb MH. (1997) Mitogen-activated protein kinase pathways. Curr. Opin. Cell Biol. 9, 180-186.

Salvato G. (2001) Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax. 56, 902-906.
Schu PV, Takegawa K, Fry MJ, Stack JH, Waterfield MD and Emr SD. (1993) Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science, 260, 88-91.
Schwartz DA. (2002) TLR4 and LPS hyporesponsiveness in humans. Int. J. Hyg. Environ. Health, 205, 221-227.
Shah BH and Catt KJ.(2002) Calcium-independent activation of extracellularly regulated kinases 1 and 2 by angiotensin II in hepatic C9 cells: roles of protein kinase C , Src/proline-rich tyrosine kinase 2, and epidermal growth receptor trans-activation. Mol. Pharmacol. 61, 343-351.
Shahrestanifar M, Fan X and Manning DR. (1999). Lysophosphatidic acid activates NF-kappaB in fibroblasts. A requirement for multiple inputs. J. Biol. Chem. 274, 3828– 3833
Siess W, Zangl KJ, Essler M, Bauer M, Brandl R, Corrinth C, Bittman R, Tigyi G and Aepfelbacheri M. (1999) Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions. Proc. Natl. Acad. Sci. USA. 96, 6931-6936.
Simeonova PP, Wang S, Hulderman T and Luster MI. (2002). c-Src-dependent activation of the epidermal growth factor receptor and mitogen-activated protein kinase pathway by arsenic. J. Biol. Chem. 25, 2945-2950.
Slaaby R, Jensen T, Harald S, Hansen M, Frohmani A and Seedorf K. (1998) PLD2 complexes with the EGF Receptor and undergoes tyrosine phosphorylation at a single site upon agonist stimulation cells. J. Biol. Chem. 273, 33722-33727.

Staal SP, Hartley JW and Rowe WP. (1977) Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma. Proc. Natl. Acad. Sci. USA, 74, 3065-3067.
Staal SP. (1987) Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary gastric adenocarcinoma. Proc. Natl. Acad. Sci. USA, 84, 5034-5037.
Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, Gaffney PR, Reese CB, McCormick F, Tempst P, Coadwell J and Hawkins PT. (1998) Protein kinase B kinases that mediate phosphatidylinositol 3,4,5- trisphosphatedependent activation of protein kinase B. Science, 279, 710-714.
Stephens L, Smrcke A, Cooke FT, Jackson TR, Sternweis PC and Hawkins PT. (1994) A novel phoshoinositide 3-kinase activity in Myeloid-derived cells is activated by G protein βγ subunits. Cell, 77, 83-93.
Stoyanov B, Volinia S, Hanck T, Rubio I, Loubtchenkov M, Malek D, Stoyanova S, Vanhaesebroeck B, Dhand R and Nurnberg B. (1995) Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science, 269, 690-693.
Swarthout JT, Doggett TA, Lemker JL and Partridge NC. (2001) Stimulation of extracellular signal-regulated kinases and proliferation in rat osteoblastic cells by parathyroid hormone is protein kinase C-dependent. J. Biol. Chem. 276, 7586-7592.
Toews ML, Ediger TL, Romberger DJ and Rennard SI. (2000) Lysophosphatidic acid in airway function and disease. Biochim. Biophys. Acta. 1582(1-3), 240-250.
Toker A and Newton AC. (2000) Cellular Signaling: Pivoting around PDK-1. Cell, 103, 185-188.
Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J and Waterfield MD. (1997) P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc. Natl. Acad. Sci. USA. 94, 4330-4335.
Venkatakrishnan G, Salgia R and Groopman JE. (2000) Chemokine Receptors CXCR-1/2 Activate Mitogen-activated Protein Kinase via the Epidermal Growth Factor Receptor in Ovarian Cancer Cells. J. Biol. Chem. 275, 6868-6875
Vrugt B, Wilson S, Bron A, Holgate ST, Djukanovic R and Aalbers R. (2000) Bronchial angiogenesis in severe glucocorticoid-dependent asthma. Eur. Respir. J. 15, 1014-1021.
Waga I, Nakamura M, Honda Z, Ferby I, Toyoshima S, Ishiguro S and Shimizu T. (1993). Two distinct signal transduction pathways for the activation of guinea-pig macrophages and neutrophils by endotoxin. Biochem. Biophys. Res. Commun. 197, 465- 471.
Wang L, Cummings R, Zhao Y, Kazlauskas A, Sham JKS, Morris A, Georas S, Brindley DN and Natarajan V. (2003) Involvement of phospholipase D2 in lysophosphatidate-induced transactivation of platelet-derived growth factor receptorβ in human bronchial epithelial cells. J. Biol. Chem. 278, 39931-39940.
Watson SP, McConnel RT and Lapetina EG. (1985) Decanoyl lysophosphatidic acid induces platelet aggregation through an extracellular action. Evidence against a second messenger role for lysophosphatidic acid. Biochem. J. 232, 61-66.
Weiner JA and Chun J (1999) Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid. Proc. Natl. Acad. Sci. 96, 5233-5238.
Wiggs BR, Bosken C, Pare PD and Hogg JC (1992) A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 145, 1251-1258.
Yamada T, Sato K, Komachi M, Malchinkhuu E, Tobo M, Kimura T, Kuwabara A, Yanagita Y, Ikeya T, Tanahashi Y, Ogawa T, Ohwada S, Morishita Y, Ohta H, Im DS, Tamoto K, Tomura H and Okajima F. (2004) Lysophosphatidic Acid (LPA) in Malignant Ascites Stimulates Motility of Human Pancreatic Cancer Cells through LPA1. J. Biol. Chem. 279, 6595-6605.
Yart A, Roche S, Wetzker R, Laffargue M, Tonks N, Mayeux P, Chap H and Raynal P. (2002) A function for phosphoinositide 3-kinase beta lipid products in coupling beta gamma to Ras activation in response to lysophosphatidic acid. J. Biol. Chem. 277, 21167-21178
Ye X, Ishii I, Kingsbury MA and Chun J. (2002) Lysophosphatidic acid as a novel cell survival/apoptotic factor. Biochim. Biophys. Acta. 1585(2-3), 108-113.
Yu J, Zhang Y, McIlroy J, Rordorf-Nikolic T, Orr GA and Backer JM. (1998) Regulation of the p85/p110 phosphatidylinositol 30-kinase: stabilization and inhibition of the p110 alpha catalytic subunit by the p85 regulatory subunit. Mol. Cell Biol. 18, 1379-1387.
Zong WX, Edelstein LC, Chen C, Bash J and Gelinas C. (1999) The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB that blocks TNFa-induced apoptosis. Genes & Dev. 13, 382-387.
Zwick E, Hackel PO, Prenzel N and Ullrich A. (1999) The EGF receptor as central transducer of heterologous signalling systems. Trends Pharmacol Sci. 20, 408-412.
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1. 9. 蘇德勝(2001),「我國職業安全衛生立法趨勢與展望」,工業安全衛生月刊。
2. 9. 蘇德勝(2001),「我國職業安全衛生立法趨勢與展望」,工業安全衛生月刊。
3. 9. 蘇德勝(2001),「我國職業安全衛生立法趨勢與展望」,工業安全衛生月刊。
4. 10. 徐堯慶(2000),「論政府採購法第五十九條第二項之妥適性問題」,律師雜誌249卷,頁3-6。
5. 10. 徐堯慶(2000),「論政府採購法第五十九條第二項之妥適性問題」,律師雜誌249卷,頁3-6。
6. 10. 徐堯慶(2000),「論政府採購法第五十九條第二項之妥適性問題」,律師雜誌249卷,頁3-6。
7. 12. 湯蘭瑞(2001),「台灣地區營造業職業災害之探討」,環保月刊第1卷第3期,頁153-159。
8. 12. 湯蘭瑞(2001),「台灣地區營造業職業災害之探討」,環保月刊第1卷第3期,頁153-159。
9. 12. 湯蘭瑞(2001),「台灣地區營造業職業災害之探討」,環保月刊第1卷第3期,頁153-159。
10. 13. 陳茂本(1999),「從ISO-9000標準談營造業之工地安全管理」,品質管制月刊第35卷第5期,頁44-53。
11. 13. 陳茂本(1999),「從ISO-9000標準談營造業之工地安全管理」,品質管制月刊第35卷第5期,頁44-53。
12. 13. 陳茂本(1999),「從ISO-9000標準談營造業之工地安全管理」,品質管制月刊第35卷第5期,頁44-53。
13. 14. 葉宏安(2000),「公共工程勞工安全衛生費用運用之探討」,工業安全衛生月刊第128期,頁15-21。
14. 14. 葉宏安(2000),「公共工程勞工安全衛生費用運用之探討」,工業安全衛生月刊第128期,頁15-21。
15. 14. 葉宏安(2000),「公共工程勞工安全衛生費用運用之探討」,工業安全衛生月刊第128期,頁15-21。