臺灣博碩士論文加值系統

本實驗評估新合成化合物 LUC 對於嗜中性白血球呼吸爆發作用的影響。LUC 以時間與濃度依存性方式抑制 formyl-Met-Leu-Phe (fMLP) 刺激大鼠嗜中性白血球產生超氧自由基，其 IC50 值為 4.5 ± 0.6 μM。LUC 抑制 fMLP 刺激嗜中性白血球產生超氧自由基的作用不具可逆性，並且對嗜中性白血球不產生細胞毒性。LUC 不會影響 phorbol 12-myristate 13-acetate (PMA) 刺激嗜中性白血球超氧自由基的生成。LUC 不會清除 dihy-droxyfurmaric acid (DHF) 自體氧化產生超氧自由基。LUC 不會影響 fMLP 刺激嗜中性白血球所產生的 p38 mitogen-activated protein kinase (MAPK)、extracellular signal-regulated kinase (ERK)、MAPK-activated protein kinase 2 (MAPKAPK2)、Akt(Thr308)、Akt(Ser473) 與 glycogen synthase kinase 3β(GSK3β) 的磷酸化作用。而LUC 會抑制蛋白質tyrosine磷酸化、phospholipase D (PLD) 的活性及細胞外 Ca2+ 流入，對這些訊息傳遞途徑的抑制作用可能參與了LUC阻斷 fMLP 刺激大鼠嗜中性白血球生成超氧自由基。

In the present study, the inhibition of superoxide anion generation by a novel synthetic compound LUC in rat neutrophils was examined. LUC inhibited formyl-Met-Leu-Phe (fMLP)-induced superoxide anion genera¬tion in a time- and concentration-dependent manner with an IC50 value of 4.5 ± 0.6 μM. LUC had no effect on phorbol 12-myristate 13-acetate (PMA)-induced response. Inhibition by LUC was irreversible and not caused by cytotoxic effect. LUC did not scavenge the generated superoxide during dihydroxyfumaric acid (DHF) autoxidation. LUC had no effect on the phosphorylation of p38 mito¬gen-activated protein kinase (MAPK)、extracellular signal-regulated kinase (ERK)、MAPK-activated protein kinase 2 (MAPKAPK2)、Akt(Thr308)、Akt(Ser473) and glycogen synthase kinase 3β(GSK3β) in response to fMLP stimulation. However, LUC attenu¬ated the fMLP-induced protein tyrosine phosphorylation and phospholipase D (PLD) activity, and blocked extracellu-lar Ca2+ entry. Inhibition of these signaling pathways is probably responsible for the inhibition of fMLP-induced superoxide anion generation by LUC in rat neutro¬phils.

目錄


縮寫表 iv
中文摘要 vi
Abstract vii
第一章　序論 1
一、 前言 1
二、 嗜中性白血球的殺菌作用 1
三、 NADPH oxidase 2
四、 MAPK 7
五、 PI3K/Akt 8
六、 Phospholipase D (PLD) 11
七、 PLC與鈣離子 12
八、 Tyrosine kinase 15
第二章　實驗材料與方法 28
一、 實驗動物 28
二、 實驗藥品 28
三、 嗜中性白血球之分離 28
四、 藥物對嗜中性白血球細胞毒性之測量 29
五、 藥物對嗜中性白血球產生超氧自由基之測量 31
六、 藥物對超氧自由基直接清除作用之測量 31
七、 LUC對fMLP刺激細胞產生超氧自由基之可逆性 32
八、 測量細胞內p38 MAPK、MAPKAPK2、ERK、Akt、GSK 3β 與 tyrosine 的磷酸化程度 32
九、 藥物對細胞內 Ca2+ 濃度之測量 33
十、 測量細胞內PLD之活性 33
十一、 統計分析 35
第三章　實驗結果 40
一、 LUC對超氧自由基生成的影響 40
二、 LUC 對嗜中性白血球的毒性 41
三、 LUC 對 DHF 自體氧化反應的影響 41
四、 LUC 對 fMLP 刺激 p38 MAPK、MAPKAPK2 與 ERK 磷酸化的影響 41
五、 LUC 對 fMLP 刺激 Akt 與 GSK 3β 磷酸化的影響 42
六、 LUC 對 fMLP 刺激蛋白質tyrosine磷酸化的影響 43
七、 LUC 對 fMLP 刺激 PLD 活性的影響 43
八、 LUC 對 fMLP 刺激 PLCCa2+ 活化的影響 43
第四章　討論和結論 59
一、 討論 59
二、 結論 62
參考文獻 64


圖表目錄


表 3-1. LUC 對嗜中性白血球的細胞毒性 58

圖 1-1. 嗜中性白血球透過趨化作用到達感染處 17
圖 1-2. 嗜中性白血球的 oxygen-independent 與 dependent 殺菌機制 18
圖 1-3. 活化的 NADPH oxidase 產生超氧自由基 19
圖 1-4. NADPH oxidase 的 p40phox、p47phox 與 p67phox domain 結構 20
圖 1-5. p38 MAPK 與 ERK 的訊息傳遞路徑 21
圖 1-6. PI3K families 的 domain 結構 22
圖 1-7. PKB/Akt、PDK1 和 GSK3 的 domain 結構 23
圖 1-8. PI3K、Akt 與 GSK3 的訊息傳遞路徑 24
圖 1-9. 哺乳動物的 PLD domain 結構 25
圖 1-10. PLC 與 PLD 的訊息傳遞路徑 26
圖 1-11. 調控細胞內 Ca2+ 濃度的機制 27
圖 2-1. 利用LDH 偵測細胞毒性之原理 36
圖 2-2. Calcein-AM 偵測細胞毒性之原理 37
圖 2-3. NBT 偵測 DHF 自體氧化產生超氧自由基之原理 38
圖 2-4. PLD 與 PLC 對 PC 之作用 39
圖 3-1. LUC 時間依存性抑制 fMLP 刺激細胞產生超氧自由基 44
圖 3-2. LUC 濃度依存性抑制 fMLP 刺激細胞產生超氧自由基 45
圖 3-3. LUC 對PMA刺激嗜中性白血球產生超氧自由基之影響 46
圖 3-4. LUC 對 fMLP 刺激細胞產生超氧自由基之可逆性 47
圖 3-5. LUC 對 DHF 自體氧化之影響 48
圖 3-6. LUC 對 fMLP 刺激 p38 MAPK 磷酸化的影響 49
圖 3-7. LUC 對 fMLP 刺激 MAPKAPK2 磷酸化的影響 50
圖 3-8. LUC 對 fMLP 刺激 ERK 磷酸化的影響 51
圖 3-9. LUC 對 fMLP 刺激 Akt(Thr308) 磷酸化的影響 52
圖 3-10. LUC 對 fMLP 刺激 Akt(Ser473) 磷酸化的影響 53
圖 3-11. LUC 對 fMLP 刺激 GSK3β 磷酸化的影響 54
圖 3-12. LUC 對 fMLP 刺激蛋白質tyrosine磷酸化的影響 55
圖 3-13. LUC 濃度依存性對 PLD 活性之影響 56
圖 3-14. LUC 對 fMLP 刺激細胞造成增加 [Ca2+]i 之影響 57
圖 4-1. LUC 對嗜中性白血球產生超氧自由基可能的影響途徑 63

Abo A, Webb MR, Grogan A, Segal AW (1994) Activation of NADPH oxidase involves the dissociation of p21rac from its inhibitory GDP/GTP ex-change protein (rhoGDI) followed by its translocation to the plasma membrane. Biochem J 298 Pt 3: 585-91.
Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hem-mings BA (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15: 6541-51.
Alessi DR, Deak M, Casamayor A, Caudwell FB, Morrice N, Norman DG, Gaffney P, Reese CB, MacDougall CN, Harbison D, Ashworth A, Bownes M (1997) 3-Phosphoinositide-dependent protein kinase-1 (PDK1): struc-tural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol 7: 776-89.
Alonso-Torre SR, Garcia-Sancho J (1997) Arachidonic acid inhibits capacita-tive calcium entry in rat thymocytes and human neutrophils. Biochim Biophys Acta 1328: 207-13.
Anderson KE, Coadwell J, Stephens LR, Hawkins PT (1998) Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to acti-vate protein kinase B. Curr Biol 8: 684-91.
Aoki J (2004) Mechanisms of lysophosphatidic acid production. Semin Cell Dev Biol 15: 477-89.
Babior BM (2004) NADPH oxidase. Curr Opin Immunol 16: 42-7.
Babior BM, Lambeth JD, Nauseef W (2002) The neutrophil NADPH oxidase. Arch Biochem Biophys 397: 342-4.
Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (2000) A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase C (PKC ) and PKC-related kinase 2 by PDK1. J Biol Chem 275: 20806-13.
Benna JE, Dang PM, Gaudry M, Fay M, Morel F, Hakim J, Gougerot-Pocidalo MA (1997) Phosphorylation of the respiratory burst oxidase subunit p67phox during human neutrophil activation. Regulation by protein kinase C-dependent and independent pathways. J Biol Chem 272: 17204-8.
Berridge MJ (1995) Capacitative calcium entry. Biochem J 312: 1-11.
Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1: 11-21
Berton G, Mocsai A, Lowell CA (2005) Src and Syk kinases: key regulators of phagocytic cell activation. Trends Immunol 26: 208-14.
Biondi RM, Cheung PC, Casamayor A, Deak M, Currie RA, Alessi DR (2000) Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA. EMBO J 19: 979-88.
Biondi RM, Kieloch A, Currie RA, Deak M, Alessi DR (2001) The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB. EMBO J 20: 4380-90.
Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348: 241-55.
Bollag WB (1998) Measurement of phospholipase D activity. Methods Mol Biol 105: 151-60.
Bolotina VM, Csutora P (2005) CIF and other mysteries of the store-operated Ca2+-entry pathway. Trends Biochem Sci 30: 378-87.
Bouin AP, Grandvaux N, Vignais PV, Fuchs A (1998) p40phox is phosphory-lated on threonine 154 and serine 315 during activation of the phagocyte NADPH oxidase. Implication of a protein kinase c-type kinase in the phosphorylation process. J Biol Chem 273: 30097-103.
Bowman EP, Uhlinger DJ, Lambeth JD (1993) Neutrophil phospholipase D is activated by a membrane-associated Rho family small molecular weight GTP-binding protein. J Biol Chem 268: 21509-12.
Bravo J, Karathanassis D, Pacold CM, Pacold ME, Ellson CD, Anderson KE, Butler PJ, Lavenir I, Perisic O, Hawkins PT, Stephens L, Williams RL (2001) The crystal structure of the PX domain from p40phox bound to phosphatidylinositol 3-phosphate. Mol Cell 8: 829-39.
Brodbeck D, Hill MM, Hemmings BA (2001) Two splice variants of protein kinase B have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site serine 472 in the car-boxyl-terminal hydrophobic domain. J Biol Chem 276: 29550-8.
Burritt JB, Foubert TR, Baniulis D, Lord CI, Taylor RM, Mills JS, Baughan TD, Roos D, Parkos CA, Jesaitis AJ (2003) Functional epitope on human neutrophil flavocytochrome b558. J Immunol 170: 6082-9.
Casamayor A, Morrice NA, Alessi DR (1999) Phosphorylation of Ser241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem J 342: 287-92.
Chan TO, Tsichlis PN (2001) PDK2: a complex tail in one Akt. Sci STKE 2001: PE1.
Chang LC, Wang JP (1999) Examination of the signal transduction pathways leading to activation of extracellular signal-regulated kinase by for-myl-methionyl-leucyl-phenylalanine in rat neutrophils. FEBS Lett 454: 165-8.
Chang LC, Wang JP (2000) Activation of p38 mitogen-activated protein kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. Eur J Pharmacol 390: 61-6.
Chen JS, Exton JH (2005) Sites on phospholipase D2 phosphorylated by PKC. Biochem Biophys Res Commun 333: 1322-6.
Chen LW, Lin MW, Hsu CM (2005) Different pathways leading to activation of extracellular signal-regulated kinase and p38 MAP kinase by for-myl-methionyl-leucyl-phenylalanine or platelet activating factor in hu-man neutrophils. J Biomed Sci 12: 311-9.
Chen Q, Powell DW, Rane MJ, Singh S, Butt W, Klein JB, McLeish KR (2003) Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J Immunol 170: 5302-8.
Ching TT, Hsu AL, Johnson AJ, Chen CS (2001) Phosphoinositide 3-kinase facilitates antigen-stimulated Ca2+ influx in RBL-2H3 mast cells via a phosphatidylinositol 3,4,5-trisphosphate-sensitive Ca2+ entry mechanism. J Biol Chem 276: 14814-20.
Chowdhury AK, Watkins T, Parinandi NL, Saatian B, Kleinberg ME, Usatyuk PV, Natarajan V (2005) Src-mediated tyrosine phosphorylation of p47phox in hyperoxia-induced activation of NADPH oxidase and generation of reactive oxygen species in lung endothelial cells. J Biol Chem 280: 20700-11.
Cole A, Frame S, Cohen P (2004) Further evidence that the tyrosine phos-phorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event. Biochem J 377: 249-55.
Colley WC, Altshuller YM, Sue-Ling CK, Copeland NG, Gilbert DJ, Jenkins NA, Branch KD, Tsirka SE, Bollag RJ, Bollag WB, Frohman MA (1997) Cloning and expression analysis of murine phospholipase D1. Biochem J 326: 745-53.
Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, Bar-Sagi D, Morris AJ, Frohman MA (1997) Phospholipase D2, a distinct phos-pholipase D isoform with novel regulatory properties that provokes cy-toskeletal reorganization. Curr Biol 7: 191-201.
Collins BJ, Deak M, Arthur JS, Armit LJ, Alessi DR (2003) In vivo role of the PIF-binding docking site of PDK1 defined by knock-in mutation. EMBO J 22: 4202-11.
Conricode KM, Brewer KA, Exton JH (1992) Activation of phospholipase D by protein kinase C. Evidence for a phosphorylation-independent mechanism. J Biol Chem 267: 7199-202.
Conus NM, Hannan KM, Cristiano BE, Hemmings BA, Pearson RB (2002) Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase. J Biol Chem 277: 38021-8.
Cook JA, Mitchell JB (1989) Viability measurements in mammalian cell sys-tems. Anal Biochem 179: 1-7.
Cross AR, Curnutte JT (1995) The cytosolic activating factors p47phox and p67phox have distinct roles in the regulation of electron flow in NADPH oxidase. J Biol Chem 270: 6543-8.
Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhi-bition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378: 785-9.
Cross MJ, Roberts S, Ridley AJ, Hodgkin MN, Stewart A, Claesson-Welsh L, Wakelam MJ (1996) Stimulation of actin stress fibre formation mediated by activation of phospholipase D. Curr Biol 6: 588-97.
Dang PM, Babior BM, Smith RM (1999) NADPH dehydrogenase activity of p67phox, a cytosolic subunit of the leukocyte NADPH oxidase. Biochem-istry 38: 5746-53.
Dang PM, Cross AR, Babior BM (2001) Assembly of the neutrophil respira-tory burst oxidase: a direct interaction between p67phox and cytochrome b558. Proc Natl Acad Sci USA 98: 3001-5.
Dang PM, Johnson JL, Babior BM (2000) Binding of nicotinamide adenine dinucleotide phosphate to the tetratricopeptide repeat domains at the N-terminus of p67phox, a subunit of the leukocyte nicotinamide adenine dinucleotide phosphate oxidase. Biochemistry 39: 3069-75.
Dang PM, Morel F, Gougerot-Pocidalo MA, Benna JE (2003) Phosphorylation of the NADPH oxidase component p67phox by ERK2 and P38 MAPK: se-lectivity of phosphorylated sites and existence of an intramolecular regulatory domain in the tetratricopeptide-rich region. Biochemistry 42: 4520-6.
Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (1998) Phos-phoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci USA 95: 11211-6.
DeLeo FR, Burritt JB, Yu L, Jesaitis AJ, Dinauer MC, Nauseef WM (2000) Processing and maturation of flavocytochrome b558 include incorporation of heme as a prerequisite for heterodimer assembly. J Biol Chem 275: 13986-93.
Dewas C, Fay M, Gougerot-Pocidalo MA, El-Benna J (2000) The mito-gen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway is involved in formyl-methionyl-leucyl-phenylalanine-induced p47phox phosphorylation in human neutrophils. J Immunol 165: 5238-44.
Dinauer MC (2005) Chronic granulomatous disease and other disorders of phagocyte function. Hematology (Am Soc Hematol Educ Program) 89-95.
Doussiere J, Brandolin G, Derrien V, Vignais PV (1993) Critical assessment of the presence of an NADPH binding site on neutrophil cytochrome b558 by photoaffinity and immunochemical labeling. Biochemistry 32: 8880-7.
Du G, Altshuller YM, Vitale N, Huang P, Chasserot-Golaz S, Morris AJ, Bader MF, Frohman MA (2003) Regulation of phospholipase D1 subcel-lular cycling through coordination of multiple membrane association motifs. J Cell Biol 162: 305-15.
Du G, Huang P, Liang BT, Frohman MA (2004) Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II receptor endocytosis. Mol Biol Cell 15: 1024-30.
Dusi S, Donini M, Rossi F (1996) Mechanisms of NADPH oxidase activation: translocation of p40phox, Rac1 and Rac2 from the cytosol to the mem-branes in human neutrophils lacking p47phox or p67phox. Biochem J 314: 409-12.
Dusi S, Rossi F (1993) Activation of NADPH oxidase of human neutrophils involves the phosphorylation and the translocation of cytosolic p67phox. Biochem J 296: 367-71.
El Benna J, Han J, Park JW, Schmid E, Ulevitch RJ, Babior BM (1996) Acti-vation of p38 in stimulated human neutrophils: phosphorylation of the oxidase component p47phox by p38 and ERK but not by JNK. Arch Bio-chem Biophys 334: 395-400.
Ellson CD, Gobert-Gosse S, Anderson KE, Davidson K, Erdjument-Bromage H, Tempst P, Thuring JW, Cooper MA, Lim ZY, Holmes AB, Gaffney PR, Coadwell J, Chilvers ER, Hawkins PT, Stephens LR (2001) PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40phox. Nat Cell Biol 3: 679-82.
Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420: 629-35.
Faris SL, Rinckel LA, Huang J, Hong YR, Kleinberg ME (1998) Phagocyte NADPH oxidase p67phox possesses a novel carboxylterminal binding site for the GTPases Rac2 and Cdc42. Biochem Biophys Res Commun 247: 271-6.
Faurschou M, Borregaard N (2003) Neutrophil granules and secretory vesicles in inflammation. Microbes Infect 5: 1317-27.
Filippa N, Sable CL, Filloux C, Hemmings B, Van Obberghen E (1999) Mechanism of protein kinase B activation by cyclic AMP-dependent protein kinase. Mol Cell Biol 19: 4989-5000.
Finegold AA, Shatwell KP, Segal AW, Klausner RD, Dancis A (1996) In-tramembrane bis-heme motif for transmembrane electron transport con-served in a yeast iron reductase and the human NADPH oxidase. J Biol Chem 271: 31021-4.
Fontayne A, Dang PM, Gougerot-Pocidalo MA, El-Benna J (2002) Phos-phorylation of p47phox sites by PKC , II, , and : effect on binding to p22phox and on NADPH oxidase activation. Biochemistry 41: 7743-50.
Forbes LV, Moss SJ, Segal AW (1999) Phosphorylation of p67phox in the neu-trophil occurs in the cytosol and is independent of p47phox. FEBS Lett 449: 225-9.
Frame S, Cohen P (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359: 1-16.
Freeman JL, Abo A, Lambeth JD (1996) Rac "insert region" is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. J Biol Chem 271: 19794-801.
Freeman JL, Kreck ML, Uhlinger DJ, Lambeth JD (1994) Ras effec-tor-homologue region on Rac regulates protein associations in the neu-trophil respiratory burst oxidase complex. Biochemistry 33: 13431-5.
Freyberg Z, Siddhanta A, Shields D (2003) "Slip, sliding away": phospholi-pase D and the Golgi apparatus. Trends Cell Biol 13: 540-6.
Freyberg Z, Sweeney D, Siddhanta A, Bourgoin S, Frohman M, Shields D (2001) Intracellular localization of phospholipase D1 in mammalian cells. Mol Biol Cell 12: 943-55.
Frieden M, James D, Castelbou C, Danckaert A, Martinou JC, Demaurex N (2004) Ca2+ homeostasis during mitochondrial fragmentation and peri-nuclear clustering induced by hFis1. J Biol Chem 279: 22704-14.
Frohman MA, Sung TC, Morris AJ (1999) Mammalian phospholipase D structure and regulation. Biochim Biophys Acta 1439: 175-86.
Fukami K (2002) Structure, regulation, and function of phospholipase C isozymes. J Biochem (Tokyo) 131: 293-9.
Gilabert JA, Parekh AB (2000) Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca2+ current I(CRAC). EMBO J 19: 6401-7.
Goldberg B, Stern A (1977) The role of the superoxide anion as a toxic spe-cies in the erythrocyte. Arch Biochem Biophys 178: 218-25.
Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3 in cellular signaling. Prog Neurobiol 65: 391-426.
Grizot S, Grandvaux N, Fieschi F, Faure J, Massenet C, Andrieu JP, Fuchs A, Vignais PV, Timmins PA, Dagher MC, Pebay-Peyroula E (2001) Small angle neutron scattering and gel filtration analyses of neutrophil NADPH oxidase cytosolic factors highlight the role of the C-terminal end of p47phox in the association with p40phox. Biochemistry 40: 3127-33.
Groemping Y, Rittinger K (2005) Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J 386: 401-16.
Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indi-cators with greatly improved fluorescence properties. J Biol Chem 260: 3440-50.
Hallett MB, Cole C, Dewitt S (2003) Detection and visualization of oxidase activity in phagocytes. Methods Mol Biol 225: 61-7.
Hallett MB, Hodges R, Cadman M, Blanchfield H, Dewitt S, Pettit EJ, Laf-fafian I, Davies EV (1999) Techniques for measuring and manipulating free Ca2+ in the cytosol and organelles of neutrophils. J Immunol Methods 232: 77-88.
Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA (1995) Human ADP-ribosylation fac-tor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J Biol Chem 270: 29640-3.
Hammond SM, Jenco JM, Nakashima S, Cadwallader K, Gu Q, Cook S, No-zawa Y, Prestwich GD, Frohman MA, Morris AJ (1997) Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding pro-teins and protein kinase C. J Biol Chem 272: 3860-8.
Han CH, Freeman JL, Lee T, Motalebi SA, Lambeth JD (1998) Regulation of the neutrophil respiratory burst oxidase. Identification of an activation domain in p67phox. J Biol Chem 273: 16663-8.
Han CH, Lee MH (2000) Activation domain in P67phox regulates the steady state reduction of FAD in gp91phox. J Vet Sci 1: 27-31.
Han JM, Kim JH, Lee BD, Lee SD, Kim Y, Jung YW, Lee S, Cho W, Ohba M, Kuroki T, Suh PG, Ryu SH (2002) Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells. J Biol Chem 277: 8290-7.
Hanada M, Feng J, Hemmings BA (2004) Structure, regulation and function of PKB/AKT-a major therapeutic target. Biochim Biophys Acta 1697: 3-16.
Heyworth PG, Bohl BP, Bokoch GM, Curnutte JT (1994) Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558. J Biol Chem 269: 30749-52.
Hill MM, Andjelkovic M, Brazil DP, Ferrari S, Fabbro D, Hemmings BA (2001) Insulin-stimulated protein kinase B phosphorylation on Ser473 is independent of its activity and occurs through a staurosporine-insensitive kinase. J Biol Chem 276: 25643-6.
Hill MM, Feng J, Hemmings BA (2002) Identification of a plasma membrane Raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1. Curr Biol 12: 1251-5.
Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D (2001) Solution structure of the PX domain, a target of the SH3 domain. Nat Struct Biol 8: 526-30.
Hirst RA, Harrison C, Hirota K, Lambert DG (1999) Measurement of [Ca2+]i in whole cell suspensions using fura-2. Methods Mol Biol 114: 31-9.
Hodgkin MN, Masson MR, Powner D, Saqib KM, Ponting CP, Wakelam MJ (2000) Phospholipase D regulation and localisation is dependent upon a phosphatidylinositol 4,5-bisphosphate-specific PH domain. Curr Biol 10: 43-6.
Honda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, Kawamoto K, Nakayama K, Morris AJ, Frohman MA, Kanaho Y (1999) Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell 99: 521-32.
Hoth M, Fanger CM, Lewis RS (1997) Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J Cell Biol 137: 633-48.
Hoyal CR, Gutierrez A, Young BM, Catz SD, Lin JH, Tsichlis PN, Babior BM (2003) Modulation of p47phox activity by site-specific phosphorylation: Akt-dependent activation of the NADPH oxidase. Proc Natl Acad Sci USA 100: 5130-5.
Huang J, Hitt ND, Kleinberg ME (1995) Stoichiometry of p22phox and gp91phox in phagocyte cytochrome b558. Biochemistry 34: 16753-7.
Huang J, Kleinberg ME (1999) Activation of the phagocyte NADPH oxidase protein p47phox. Phosphorylation controls SH3 domain-dependent binding to p22phox. J Biol Chem 274: 19731-7.
Hubbard SR, Till JH (2000) Protein tyrosine kinase structure and function. Annu Rev Biochem 69: 373-98.
Itagaki K, Hauser CJ (2003) Sphingosine 1-phosphate, a diffusible calcium influx factor mediating store-operated calcium entry. J Biol Chem 278: 27540-7.
Itagaki K, Kannan KB, Hauser CJ (2005) Lysophosphatidic acid triggers cal-cium entry through a non-store-operated pathway in human neutrophils. J Leukoc Biol 77: 181-9.
Ito T, Nakamura R, Sumimoto H, Takeshige K, Sakaki Y (1996) An SH3 do-main-mediated interaction between the phagocyte NADPH oxidase fac-tors p40phox and p47phox. FEBS Lett 385: 229-32.
James SR, Downes CP, Gigg R, Grove SJ, Holmes AB, Alessi DR (1996) Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem J 315 ( Pt 3): 709-13.
Jenkins GM, Frohman MA (2005) Phospholipase D: a lipid centric review. Cell Mol Life Sci 62: 2305-16.
Kanai F, Liu H, Field SJ, Akbary H, Matsuo T, Brown GE, Cantley LC, Yaffe MB (2001) The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Nat Cell Biol 3: 675-8.
Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Wil-liams RL (2002) Binding of the PX domain of p47phox to phosphatidy-linositol 3,4-bisphosphate and phosphatidic acid is masked by an in-tramolecular interaction. EMBO J 21: 5057-68.
Katan M, Williams RL (1997) Phosphoinositide-specific phospholipase C: structural basis for catalysis and regulatory interactions. Semin Cell Dev Biol 8: 287-296.
Kim C, Dinauer MC (2001) Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in re-sponse to specific signaling pathways. J Immunol 166: 1223-32.
Kim JH, Kim Y, Lee SD, Lopez I, Arnold RS, Lambeth JD, Suh PG, Ryu SH (1999) Selective activation of phospholipase D2 by unsaturated fatty acid. FEBS Lett 454: 42-6.
Knaus UG, Morris S, Dong HJ, Chernoff J, Bokoch GM (1995) Regulation of human leukocyte p21-activated kinases through G protein-coupled re-ceptors. Science 269: 221-3..
Kobayashi T, Cohen P (1999) Activation of serum- and glucocorti-coid-regulated protein kinase by agonists that activate phosphatidy-linositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem J 339 ( Pt 2): 319-28.
Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, Sumimoto H (1999) Tetratricopeptide repeat (TPR) motifs of p67phox participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem 274: 25051-60.
Kook S, Exton JH (2005) Identification of interaction sites of protein kinase C on phospholipase D1. Cell Signal 17: 1423-32.
Koshkin V, Lotan O, Pick E (1997) Electron transfer in the superox-ide-generating NADPH oxidase complex reconstituted in vitro. Biochim Biophys Acta 1319: 139-46.
Kostellow AB, Ma GY, Morrill GA (1996) Progesterone triggers the rapid ac-tivation of phospholipase D in the amphibian oocyte plasma membrane when initiating the G2/M transition. Biochim Biophys Acta 1304: 263-71.
Koyasu S (2003) The role of PI3K in immune cells. Nat Immunol 4: 313-9.
Kramer RM, Roberts EF, Manetta J, Putnam JE (1991) The Ca2+-sensitive cytosolic phospholipase A2 is a 100-kDa protein in human monoblast U937 cells. J Biol Chem 266: 5268-72.
Kuan YH, Lin RH, Tsao LT, Chen YL, Tzeng CC, Wang JP (2005) Inhibition of phospholipase D activation by CYL-26z in formyl peptide-stimulated neutrophils involves the blockade of RhoA activation. Biochem Phar-macol 70: 901-10.
Kuribayashi F, Nunoi H, Wakamatsu K, Tsunawaki S, Sato K, Ito T, Sumi-moto H (2002) The adaptor protein p40phox as a positive regulator of the superoxide-producing phagocyte oxidase. EMBO J 21: 6312-20.
Kusner DJ, Hall CF, Schlesinger LS (1996) Activation of phospholipase D is tightly coupled to the phagocytosis of Mycobacterium tuberculosis or opsonized zymosan by human macrophages. J Exp Med 184: 585-95.
Lawson MA, Maxfield FR (1995) Ca2+- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature 377: 75-9.
Leavey PJ, Gonzalez-Aller C, Thurman G, Kleinberg M, Rinckel L, Ambruso DW, Freeman S, Kuypers FA, Ambruso DR (2002) A 29-kDa protein associated with p67phox expresses both peroxiredoxin and phospholipase A2 activity and enhances superoxide anion production by a cell-free sys-tem of NADPH oxidase activity. J Biol Chem 277: 45181-7.
Leto TL, Adams AG, de Mendez I (1994) Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline-rich targets. Proc Natl Acad Sci U S A 91: 10650-4.
Leusen JH, Bolscher BG, Hilarius PM, Weening RS, Kaulfersch W, Seger RA, Roos D, Verhoeven AJ (1994) 156ProGln substitution in the light chain of cytochrome b558 of the human NADPH oxidase p22phox leads to defec-tive translocation of the cytosolic proteins p47phox and p67phox. J Exp Med 180: 2329-34.
Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D (2000) Roles of PLC2 and 3 and PI3K in chemoattractant-mediated signal transduction. Science 287: 1046-9.
Lietzke SE, Bose S, Cronin T, Klarlund J, Chawla A, Czech MP, Lambright DG (2000) Structural basis of 3-phosphoinositide recognition by pleck-strin homology domains. Mol Cell 6: 385-94.
Lopes LR, Dagher MC, Gutierrez A, Young B, Bouin AP, Fuchs A, Babior BM (2004) Phosphorylated p40phox as a negative regulator of NADPH oxidase. Biochemistry 43: 3723-30.
Lopez I, Arnold RS, Lambeth JD (1998) Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regu-lates hPLD2. J Biol Chem 273: 12846-52.
Low AM (1996) Role of tyrosine kinase on Ca2+ entry and refilling of ago-nist-sensitive Ca2+ stores in vascular smooth muscles. Can J Physiol Pharmacol 74: 298-304.
Massenet C, Chenavas S, Cohen-Addad C, Dagher MC, Brandolin G, Pe-bay-Peyroula E, Fieschi F (2005) Effects of p47phox C terminus phos-phorylations on binding interactions with p40phox and p67phox. Structural and functional comparison of p40phox and p67phox SH3 domains. J Biol Chem 280: 13752-61.
Matute JD, Arias AA, Dinauer MC, Patino PJ (2005) p40phox: the last NADPH oxidase subunit. Blood Cells Mol Dis 35: 291-302.
Mayer-Scholl A, Averhoff P, Zychlinsky A (2004) How do neutrophils and pathogens interact?. Curr Opin Microbiol 7: 62-6.
McFadzean I, Gibson A (2002) The developing relationship between recep-tor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol 135: 1-13.
Mignen O, Thompson JL, Yule DI, Shuttleworth TJ (2005) Agonist activation of arachidonate-regulated Ca2+-selective (ARC) channels in murine pa-rotid and pancreatic acinar cells. J Physiol 564: 791-801.
Mora A, Komander D, van Aalten DM, Alessi DR (2004) PDK1, the master regulator of AGC kinase signal transduction. Semin Cell Dev Biol 15: 161-70.
Morris AJ, Frohman MA, Engebrecht J (1997) Measurement of phospholipase D activity. Anal Biochem 252: 1-9.
Neri S, Mariani E, Meneghetti A, Cattini L, Facchini A (2001) Cal-cein-acetyoxymethyl cytotoxicity assay: standardization of a method al-lowing additional analyses on recovered effector cells and supernatants. Clin Diagn Lab Immunol 8: 1131-5.
Nisimoto Y, Freeman JL, Motalebi SA, Hirshberg M, Lambeth JD (1997) Rac binding to p67phox. Structural basis for interactions of the Rac1 effector region and insert region with components of the respiratory burst oxidase. J Biol Chem 272: 18834-41.
Nisimoto Y, Motalebi S, Han CH, Lambeth JD (1999) The p67phox activation domain regulates electron flow from NADPH to flavin in flavocyto-chrome b558. J Biol Chem 274: 22999-3005.
Nisimoto Y, Otsuka-Murakami H, Lambeth DJ (1995) Reconstitution of fla-vin-depleted neutrophil flavocytochrome b558 with 8-mercapto-FAD and characterization of the flavin-reconstituted enzyme. J Biol Chem 270: 16428-34.
Nusse O, Serrander L, Foyouzi-Youssefi R, Monod A, Lew DP, Krause KH (1997) Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes. J Biol Chem 272: 28360-7.
Palicz A, Foubert TR, Jesaitis AJ, Marodi L, McPhail LC (2001) Phosphatidic acid and diacylglycerol directly activate NADPH oxidase by interacting with enzyme components. J Biol Chem 276: 3090-7.
Parekh AB, Putney JW Jr (2005) Store-operated calcium channels. Physiol Rev 85: 757-810.
Patterson RL, van Rossum DB, Gill DL (1999) Store-operated Ca2+ entry: evidence for a secretion-like coupling model. Cell 98: 487-99.
Perez-Garcia MJ, Cena V, de Pablo Y, Llovera M, Comella JX, Soler RM (2004) Glial cell line-derived neurotrophic factor increases intracellular calcium concentration. Role of calcium/calmodulin in the activation of the phosphatidylinositol 3-kinase pathway. J Biol Chem 279: 6132-42.
Peterson RT, Schreiber SL (1999) Kinase phosphorylation: keeping it all in the family. Curr Biol 9: R521-4.
Poinas A, Gaillard J, Vignais P, Doussiere J (2002) Exploration of the diaphorase activity of neutrophil NADPH oxidase. Eur J Biochem 269: 1243-52.
Ponting CP, Ito T, Moscat J, Diaz-Meco MT, Inagaki F, Sumimoto H (2002) OPR, PC and AID: all in the PB1 family. Trends Biochem Sci 27: 10.
Ponting CP, Kerr ID (1996) A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identi-fication of duplicated repeats and potential active site residues. Protein Sci 5: 914-22.
Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G (1998) Phosphorylation and activation of p70s6k by PDK1. Science 279: 707-10.
Putney JW Jr (1990) Capacitative calcium entry revisited. Cell Calcium 11: 611-24.
Putney JW Jr, Broad LM, Braun FJ, Lievremont JP, Bird GS (2001) Mecha-nisms of capacitative calcium entry. J Cell Sci 114: 2223-9.
Randriamampita C, Tsien RY (1993) Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature 364: 809-14.
Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR (2001) p38 kinase-dependent MAPKAPK-2 activation func-tions as 3-phosphoinositide-dependent kinase-2 for Akt in human neu-trophils. J Biol Chem 276: 3517-23.
Reeves EP, Lu H, Jacobs HL, Messina CG, Bolsover S, Gabella G, Potma EO, Warley A, Roes J, Segal AW (2002) Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416: 291-7.
Regier DS, Waite KA, Wallin R, McPhail LC (1999) A phosphatidic acid-activated protein kinase and conventional protein kinase C isoforms phosphorylate p22phox, an NADPH oxidase component. J Biol Chem 274: 36601-8.
Rhee SG (2001) Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 70: 281-312.
Roden MM, Lee KH, Panelli MC, Marincola FM (1999) A novel cytolysis assay using fluorescent labeling and quantitative fluorescent scanning technology. J Immunol Methods 226: 29-41.
Sasaki T, Kawai K, Saijo-Kurita K, Ohno T (1992) Detergent cytotoxicity: simplified assay of cytolysis by measuring LDH activity. Toxicology in Vitro 6: 451.
Sayeed MM (2000) Exuberant Ca2+ signaling in neutrophils: a cause for con-cern. News Physiol Sci 15: 130-136.
Sciorra VA, Rudge SA, Prestwich GD, Frohman MA, Engebrecht J, Morris AJ (1999) Identification of a phosphoinositide binding motif that mediates activation of mammalian and yeast phospholipase D isoenzymes. EMBO J 18: 5911-21.
Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23: 197-223.
Shaw M, Cohen P, Alessi DR (1998) The activation of protein kinase B by H2O2 or heat shock is mediated by phosphoinositide 3-kinase and not by mitogen-activated protein kinase-activated protein kinase-2. Biochem J 336 ( Pt 1): 241-6.
Sheppard FR, Kelher MR, Moore EE, McLaughlin NJ, Banerjee A, Silliman CC (2005) Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation. J Leu-koc Biol 78: 1025-42.
Shibata K, Morita K, Kitayama S, Okamoto H, Dohi T (1996) Ca2+ entry in-duced by calcium influx factor and its regulation by protein kinase C in rabbit neutrophils. Biochem Pharmacol 52: 167-71.
Shibata K, Warbington ML, Gordon BJ, Kurihara H, Van Dyke TE (2000) Defective calcium influx factor activity in neutrophils from patients with localized juvenile periodontitis. J Periodontol 71: 797-802.
Shmelzer Z, Haddad N, Admon E, Pessach I, Leto TL, Eitan-Hazan Z, Hershfinkel M, Levy R (2003) Unique targeting of cytosolic phospholi-pase A2 to plasma membranes mediated by the NADPH oxidase in phagocytes. J Cell Biol 162: 683-92.
Shukla SD, Sun GY, Gibson Wood W, Savolainen MJ, Alling C, Hoek JB (2001) Ethanol and lipid metabolic signaling. Alcohol Clin Exp Res 25: 33S-39S.
Shuttleworth TJ, Thompson JL, Mignen O (2004) ARC channels: a novel pathway for receptor-activated calcium entry. Physiology (Bethesda) 19: 355-61.
Silliman CC, Ambruso DR, Boshkov LK (2005) Transfusion-related acute lung injury. Blood 105: 2266-73.
Simpson AW (1999) Fluorescent measurement of [Ca2+]c. Basic practical considerations. Methods Mol Biol 114: 3-30.
Smani T, Zakharov SI, Csutora P, Leno E, Trepakova ES, Bolotina VM (2004) A novel mechanism for the store-operated calcium influx pathway. Nat Cell Biol 6: 113-20.
Someya A, Nagaoka I, Nunoi H, Yamashita T (1996) Translocation of guinea pig p40phox during activation of NADPH oxidase. Biochim Biophys Acta 1277: 217-25.
Someya A, Nunoi H, Hasebe T, Nagaoka I (1999) Phosphorylation of p40phox during activation of neutrophil NADPH oxidase. J Leukoc Biol 66: 851-7.
Song G, Ouyang G, Bao S (2005) The activation of Akt/PKB signaling path-way and cell survival. J Cell Mol Med 9: 59-71.
Stahelin RV, Ananthanarayanan B, Blatner NR, Singh S, Bruzik KS, Murray D, Cho W (2004) Mechanism of membrane binding of the phospholipase D1 PX domain. J Biol Chem 279: 54918-26.
Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, Gaffney PR, Reese CB, McCormick F, Tempst P, Coadwell J, Hawkins PT (1998) Protein kinase B kinases that mediate phosphatidy-linositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science 279: 710-4.
Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, McCormick F, Hawkins PT (1997) Dual role of phosphati-dylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277: 567-70.
Suh CI, Stull N, Fuji Y, Grinstein S, Yaffe M, Atkinson S, Dinauer MC (2004) Role for p40phox in Fc-receptor-induced NADPH oxidase activation. Blood 104: 653.
Sung TC, Altshuller YM, Morris AJ, Frohman MA (1999) Molecular analysis of mammalian phospholipase D2. J Biol Chem 274: 494-502.
Sung TC, Zhang Y, Morris AJ, Frohman MA (1999) Structural analysis of human phospholipase D1. J Biol Chem 274: 3659-66.
Tintinger G, Steel HC, Anderson R (2005) Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control. Clin Exp Immunol 141: 191-200.
Tiruppathi C, Minshall RD, Paria BC, Vogel SM, Malik AB (2002) Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 39: 173-85.
Toker A, Newton AC (2000) Akt/protein kinase B is regulated by autophos-phorylation at the hypothetical PDK-2 site. J Biol Chem 275: 8271-4.
Torres M, Hall FL, O'Neill K (1993) Stimulation of human neutrophils with formyl-methionyl-leucyl-phenylalanine induces tyrosine phosphorylation and activation of two distinct mitogen-activated protein-kinases. J Im-munol 150: 1563-77.
Tsang KS, Li CK, Wong AP, Leung Y, Lau TT, Li K, Shing MM, Chik KW, Yuen PM (1999) Processing of major ABO-incompatible bone marrow for transplantation by using dextran sedimentation. Transfusion 39: 1212-9.
Tsunawaki S, Mizunari H, Nagata M, Tatsuzawa O, Kuratsuji T (1994) A novel cytosolic component, p40phox, of respiratory burst oxidase associ-ates with p67phox and is absent in patients with chronic granulomatous disease who lack p67phox. Biochem Biophys Res Commun 199: 1378-87.
Tsunawaki S, Yoshikawa K (2000) Relationships of p40phox with p67phox in the activation and expression of the human respiratory burst NADPH oxidase. J Biochem 128: 777-83.
Uings IJ, Thompson NT, Randall RW, Spacey GD, Bonser RW, Hudson AT, Garland LG. (1992) Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neu-trophil. Biochem J 281:597-600.
Ullrich A, Schlessinger J (1990) Signal transduction by receptors with tyro-sine kinase activity. Cell 61: 203-12.
van Bruggen R, Anthony E, Fernandez-Borja M, Roos D (2004) Continuous translocation of Rac2 and the NADPH oxidase component p67phox during phagocytosis. J Biol Chem 279: 9097-102.
van Weeren PC, de Bruyn KM, de Vries-Smits AM, van Lint J, Burgering BM (1998) Essential role for protein kinase B (PKB) in insulin-induced gly-cogen synthase kinase 3 inactivation. Characterization of domi-nant-negative mutant of PKB. J Biol Chem 273: 13150-6.
Vanden Abeele F, Lemonnier L, Thebault S, Lepage G, Parys JB, Shuba Y, Skryma R, Prevarskaya N (2004) Two types of store-operated Ca2+ channels with different activation modes and molecular origin in LNCaP human prostate cancer epithelial cells. J Biol Chem 279: 30326-37.
Vanhaesebroeck B, Alessi DR (2000) The PI3K-PDK1 connection: more than just a road to PKB. Biochem J 346 Pt 3: 561-76.
Waite KA, Wallin R, Qualliotine-Mann D, McPhail LC (1997) Phosphatidic acid-mediated phosphorylation of the NADPH oxidase component p47phox. Evidence that phosphatidic acid may activate a novel protein kinase. J Biol Chem 272: 15569-78.
Walker SJ, Brown HA (2004) Measurement of G protein-coupled recep-tor-stimulated phospholipase D activity in intact cells. Methods Mol Biol 237: 89-97.
Wallach TM, Segal AW (1997) Analysis of glycosylation sites on gp91phox, the flavocytochrome of the NADPH oxidase, by site-directed mutagenesis and translation in vitro. Biochem J 321 ( Pt 3): 583-5.
Wang JP, Chang LC, Hsu MF, Lin CN (2003) The blockade of formyl pep-tide-induced respiratory burst by 2',5'-dihydroxy-2-furfurylchalcone in-volves phospholipase D signaling in neutrophils. Naunyn Schmiedebergs Arch Pharmacol 368: 166-74.
Wang JP, Chang LC, Raung SL, Hsu MF, Chen CM (2002) Cellular mecha-nisms of inhibition of superoxide anion generation in rat neutrophils by the synthetic isoquinoline DMDI. Eur J Pharmacol 434: 9-16.
Wang JP, Chang LC, Raung SL, Hsu MF, Huang LJ, Kuo SC (2002) Inhibition of superoxide anion generation by YC-1 in rat neutrophils through cyclic GMP-dependent and -independent mechanisms. Biochem Pharmacol 63: 577-85.
Wang JP, Chen YS, Tsai CR, Huang LJ, Kuo SC (2004) The blockade of cyclopiazonic acid-induced store-operated Ca2+ entry pathway by YC-1 in neutrophils. Biochem Pharmacol 68: 2053-64.
Wick MJ, Ramos FJ, Chen H, Quon MJ, Dong LQ, Liu F (2003) Mouse 3-phosphoinositide-dependent protein kinase-1 undergoes dimerization and trans-phosphorylation in the activation loop. J Biol Chem 278: 42913-9.
Wientjes FB, Reeves EP, Soskic V, Furthmayr H, Segal AW (2001) The NADPH oxidase components p47phox and p40phox bind to moesin through their PX domain. Biochem Biophys Res Commun 289: 382-8.
Wientjes FB, Segal AW (2003) PX domain takes shape. Curr Opin Hematol 10: 2-7.
Wilson MI, Gill DJ, Perisic O, Quinn MT, Williams RL (2003) PB1 do-main-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62. Mol Cell 12: 39-50.
Woodgett JR (1990) Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J 9: 2431-8.
Woodgett JR (2005) Recent advances in the protein kinase B signaling path-way. Curr Opin Cell Biol 17: 150-7.
Yamazaki M, Zhang Y, Watanabe H, Yokozeki T, Ohno S, Kaibuchi K, Shi-bata H, Mukai H, Ono Y, Frohman MA, Kanaho Y (1999) Interaction of the small G protein RhoA with the C terminus of human phospholipase D1. J Biol Chem 274: 6035-8.
Yang J, Cron P, Good VM, Thompson V, Hemmings BA, Barford D (2002) Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP. Nat Struct Biol 9: 940-4.
Yang J, Cron P, Thompson V, Good VM, Hess D, Hemmings BA, Barford D (2002) Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation. Mol Cell 9: 1227-40.
Yao Y, Ferrer-Montiel AV, Montal M, Tsien RY (1999) Activation of store-operated Ca2+ current in Xenopus oocytes requires SNAP-25 but not a diffusible messenger. Cell 98: 475-85.
Yu L, Quinn MT, Cross AR, Dinauer MC (1998) Gp91phox is the heme binding subunit of the superoxide-generating NADPH oxidase. Proc Natl Acad Sci USA 95: 7993-8.
Zhan Y, He D, Newburger PE, Zhou GW (2004) p47phox PX domain of NADPH oxidase targets cell membrane via moesin-mediated association with the actin cytoskeleton. J Cell Biochem 92: 795-809.
Zhan Y, Virbasius JV, Song X, Pomerleau DP, Zhou GW (2002) The p40phox and p47phox PX domains of NADPH oxidase target cell membranes via direct and indirect recruitment by phosphoinositides. J Biol Chem 277: 4512-8.
Zubov AI, Kaznacheeva EV, Nikolaev AV, Alexeenko VA, Kiselyov K, Muallem S, Mozhayeva GN (1999) Regulation of the miniature plasma membrane Ca2+ channel I(min) by inositol 1,4,5-trisphosphate receptors. J Biol Chem 274: 25983-5.