跳到主要內容

臺灣博碩士論文加值系統

(34.204.198.73) 您好!臺灣時間:2024/07/19 14:15
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:徐銘佛
研究生(外文):Ming-Fo Hsu
論文名稱:應用化學標定法研究一氧化氮對酪胺酸磷酸水解酶的活性調控以促進胰島素的感受性
論文名稱(外文):Chemical Probe-Based Approach to Delineate the Underlying Mechanism for Nitric Oxide-Mediated Inactivation of Protein Tyrosine Phosphatases in Regulation of Insulin Signaling
指導教授:孟子青孟子青引用關係
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:105
中文關鍵詞:蛋白質酪胺酸磷酸水解酶低解離常數值半胱胺酸酪胺酸磷酸化修飾氫硫基反應的探針亞硝基化修飾胰島素一氧化氮
外文關鍵詞:protein tyrosine phosphataseactive site Cyslow pKatyrosine phosphorylationIodoacetyl-PEO-Biotin probeS-nitrosylationnitric oxideinsulin
相關次數:
  • 被引用被引用:1
  • 點閱點閱:192
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
歸類在蛋白質酪胺酸磷酸水解酶家族中的一些酵素,已知參與許多生物細胞功能過程間的調控。這類酵素的催化能力是基於具有低解離常數值特性的半胱胺酸,使得酵素在細胞生理環境中可以對受質的酪胺酸磷酸化修飾進行水解作用。蛋白質酪胺酸磷酸水解酶功能的失調會造成異常的酪胺酸磷酸信號,這關係到人類疾病像是癌症與糖尿病的成因。然而,對於標定蛋白質酪胺酸磷酸水解酶來說,現今仍缺乏高效能且可以便利使用的方法。在本論文裡,我們先建立一個新的實驗方法,使用市面上販售會與半胱胺酸其氫硫基反應的探針,在複雜的細胞環境中對蛋白質酪胺酸磷酸水解酶進行標定。基於前述低解離常數值的特性,我們預期酸性的環境條件可能有助於標定反應專一發生在蛋白質酪胺酸磷酸水解酶的半胱胺酸上。的確,即使有大量的BSA與Catalase蛋白質干擾,我們發現ㄧ個帶有PEO修飾的探針在酸鹼值6的條件下還是能夠有效對PTP1B進行標定。我們接著使用此探針來標定與分離細胞內生的蛋白質酪胺酸磷酸水解酶,結果顯示一些表現在Caco-2或是EA.hy926細胞中的蛋白質酪胺酸磷酸水解酶確實可以被分離。在下一個階段的研究裡,我們使用前述的分析技術平台來探討可能參與調控丁酸鈉誘發Caco-2細胞分化的蛋白質酪胺酸磷酸水解酶。結果顯示TC-PTP在Caco-2細胞的分化控制上,可能扮演一個未知的負向調控角色。我們進一步觀察得知,高量表現額外的TC-PTP會妨礙丁酸鈉處理的Caco-2細胞進行分化。最後,我們的分析技術平台應用在蛋白質酪胺酸磷酸水解酶其亞硝基化修飾的特性探討。初步的實驗結果顯示,探針能夠標定有活性的還原態而不是失活性的亞硝基化態PTP1B。接下來,我們檢視由胰島素刺激產生的大量ㄧ氧化氮對於細胞內生的蛋白質酪胺酸磷酸水解酶其調控作用。結果顯示SHP-1、SHP-2與PTP1B其執行酵素催化功能的半胱胺酸可能受到一氧化氮引發的亞硝基化修飾,而更進一步的活性試驗亦證實該酵素的失活。我們亦觀察到胰島素受器以及下游的分子IRS-1與PKB/Akt其酪胺酸的磷酸化修飾增多與一氧化氮有相關性,顯示一氧化氮在調控胰島素的感受性有著關鍵的角色。因此,搭配化學探針所發展的分析平台,我們驗證在胰島素刺激下而產生的ㄧ氧化氮會造成蛋白質酪胺酸磷酸水解酶的失活作用以促進胰島素感受性。
Enzymes in the protein tyrosine phosphatase (PTP) superfamily are involved in the regulation of many aspects of biological processes. The catalytic activity of PTPs is mediated by an invariant Cys residue, which has a remarkably low pKa, therefore being able to carry out nucleophilic attack on a substrate, leading to Tyr dephosphorylation. Dysfunction of PTPs results in aberrant tyrosine phosphorylation signaling which has been linked to the etiology of several human diseases, including cancer and diabetes. However, a high efficient and convenient tool for tagging PTPs as a whole is still lacking at the present time. Here, we first established a novel strategy that tags PTPs in a complicated proteome by using a commercial Iodoacetyl-PEO-Biotin probe (the PEO probe) under acidic conditions. We proposed that a low pH condition might facilitate the specificity of labeling reaction towards the active site Cys of PTPs, due to its low pKa character. Indeed, we found that the purified human PTP1B, a prototype of PTP enzymes, could be efficiently alkylated by the PEO probe at as low as pH 6.0 even in a protein mixture with excess amounts of BSA and Catalase. We then applied this probe to tag and isolate endogenous PTPs, and the results show that a number of PTPs expressed in Caco-2 or EA.hy926 cells were appeared in the pull-down fraction. In the second part of our study, the analytic pulldown platform was used to tag endogenous PTPs involved in the regulation of sodium butyrate (NaB)-induced Caco-2 cell differentiation. Our results demonstrated a novel role of TC-PTP as a negative regulator in the control of differentiation in Caco-2 cells. We further observed that a high level of ectopically expressed TC-PTP prevented Caco-2 cells from the entry of differentiation in NaB-treated cells. In the next phase of study, our strategy was applied for the characterization of S-nitrosylation on PTPs. We showed that, not only purified PTP1B but also endogenous PTPs were susceptible to nitric oxide (NO)-mediated S-nitrosylation and inactivation. Our data indicated that multiple cellular PTPs are likely S-nitrosylated at the active site Cys residue concomitantly with a burst of intrinsic NO production. We also observed a critical role of NO in insulin responsiveness, as evidenced by an NO-dependent increase of tyrosine phosphorylation levels of the insulin receptor and its downstream effectors IRS-1 and PKB/AKT. Employing the chemical probe-based approach, we demonstrated that NO mediates the inhibition of insulin receptor PTPs, leading to the enhancement of insulin responsiveness.
謝誌……………………………………………………………………..…..i
摘要…………………..………………………...……..………...……….....ii
ABSTRACT…………………………………………………...……….….iii
LIST OF CONTENTS…………………...……………………....…..……iv

CHAPTER 1: INTRODUCTION……………...…………...……….……..1
1.1 Perspective………………………………………………...……....……..2
1.2 The PTP superfamily………………………………………...……..……..2
1.3 The character of the active site Cys in PTPs……………………...………...4
1.4 The oxidation-induced PTP inactivation…………………………...…….....4
1.5 The PTP-related diseases………………………………………….....……6
1.6 The techniques used to label the reduced form of PTPs…………….…..…...8
1.7 The nitric oxide (NO)……..……………………………………….….......9
1.8 The intracellular actions of NO..………………………..………………..10
1.9 The S-nitrosylation of proteins…………………………………...…...….11
1.10 The function of protein S-nitrosylation………………...…………...…....12
1.11 The insulin signaling and NO production……………………….…...…..14
1.12 The relationship of NO and insulin resistance………………….....….…..15
1.13 The S-nitrosylation of PTPs…………………………………...…..…....16
1.14 Specific aims…………………………………...…………...……….....17

CHAPTER 2: MATERIALS AND METHODS……………..………..….19
2.1 Reagents……………..……………………………………...….……….20
2.2 Cell culture…………………………..………………………....….……21
2.3 Transient cell transfection…………...………..………………….……...21
2.4 Immunoprecipitation…………………………..….…………….……....22
2.5 Labeling of recombinant PTP1B………………...……………………….22
2.6 Isolation of PEO probe-labeled proteins…………...…………………...…23
2.7 In-gel PTP activity assay…………………………...………………...…..23
2.8 Alkaline phosphatase (ALP) assay…………………...…………………...23
2.9 Liquid phosphatase activity assay……………………...………………....24

CHAPTER 3: RESULTS AND DISCUSSION…………..………............25
3.1 Establishment of a novel strategy for isolation of cellular PTPs by using commercial Cys sulfhydryl-reacted probes…............................................26
3.1.1 The Iodoacetyl-PEO-Biotin is a probe to tag the active site Cys of recombinant PTP1B specifically under pH 6.0 condition………………….……...…….26
3.1.2 The PEO probe recognizes PTPs in complicated protein environment……......28
3.1.3 Discussion…………………………………..…………………………29

3.2 Validation of the PEO probe-based pulldown assay to identify the regulatory role of TC-PTP in NaB-treated Caco-2 cells………………………..….…31
3.2.1 The cellular TC-PTP is down-regulated in the NaB-treated Caco-2 cells…...…31
3.2.2 The novel role of TC-PTP as negative regulator during NaB treatment in Caco-2 Cells…………………………….……………………………………33
3.2.3 Discussion…………………………………………………………......34



3.3 Application of the chemical probe-based assay to quantify the S-nitrosylation of cellular PTPs in the context of insulin signaling ……...…..……………...36
3.3.1 PTPs are less susceptible to probe labeling under NO donor treatment or ATP-induced intrinsic NO production……………………..…………….36
3.3.2 The eNOS-induced NO production enhanced pTyr of insulin receptor in signaling response to insulin stimulation………..…………………………..…….38
3.3.3. A critical role of NO-mediated inactivation of endogenous PTPs in enhanced insulin responsiveness…………………………………………...…….40
3.3.4 Activation of eNOS enhanced phosphorylation of IRS-1 and PKB/Akt in signaling response to a physiological level of insulin………………………...…….42
3.3.5 Endogenous eNOS is essential for activation of insulin-induced signaling in endothelial cells……………………...……………………………….44
3.3.6 Discussion…………...……………………………………..………….45

CHAPTER 4: SUMMARY AND FUTURE STUDIES………..…...…….51
4.1 Summary…………………………………………………....………….52
4.2 Future studies………………………………………..……....………….54

CHAPTER 5: FIGURES…………….…...……………………………….57
Figure 1. The reduced form of recombinant PTP1B is alkylated by iodoacetamide to lose phosphatase activity………………………………………..58
Figure 2. Schematic illustration of the PTP-labeling workflow used to determine a condition for specific biotinylation of the active site Cys…………….59
Figure 3. Iodoacetyl-PEO-Biotin is the probe to label specifically the active site Cys of PTP1B under acidic condition……………………………...…...60
Figure 4. The PEO probe labels the active site Cys of PTP1B under acidic condition as low as pH 6.0………………..……………………….61
Figure 5. PTP1B is labeled specifically by the PEO probe in a protein mixture....62
Figure 6. The PEO probe recognizes proteins with low pKa Cys residue in cell lysates………………………………………………………...….63
Figure 7. The pY level is increased in Caco-2 cells under NaB treatment.............64
Figure 8. The reduced form of endogenous TC-PTP is decreased in NaB-treated Caco-2 cells……………………...…………………………...…..65
Figure 9. The protein level of endogenous TC-PTP is decreased in NaB-treated Caco-2 cells……………………………………………..………..66
Figure 10. NaB accelerates the decrease of TC-PTP and induces the ALP activity in Caco-2 cells……………..………………………………………67
Figure 11. The protein level of TC45 is decreased during NaB treatment in Caco-2 cells……………………………..………………………………68
Figure 12. The NaB-induced ALP activity is attenuated in TC45-transfected Caco-2 cells……………………………..……………………....69
Figure 13. The ectopically expressed TC45, not PTP1B, diminishes the ALP activity in NaB-treated Caco-2 cells………………………………70
Figure 14. The NaB-induced increase of pY signal is diminished in TC45- transfected Caco-2 cells……………………………………….…71
Figure 15. The PEO probe recognizes the reduced form but not the oxidized or S-nitrosylated form of PTP1B…………………………….……...72
Figure 16. The reduced forms of endogenous PTPs are decreased in CSNO-treated EA.hy926 cells…………………………………...……………...73
Figure 17. ATP-stimulated activation of eNOS decreases the reduced forms of endogenous PTPs in COS-7 cells……………….………………...74
Figure 18. Schematic illustration of the hypothesis that NO might enhance insulin signaling through the PTP inactivation…………………………...75
Figure 19. Insulin-induced Tyr phosphorylation is enhanced in CSNO-treated COS-7 cells……………………………………………………...76
Figure 20. The ectopically expressed eNOS is activated by insulin stimulation in COS-7 cells……………………………………………………...77
Figure 21. Insulin stimulation enhances some pY signals in eNOS-transfected COS-7 cells…………………………………...…………………78
Figure 22. The Tyr phosphorylation of insulin receptor is enhanced by insulin stimulation in eNOS-transfected COS-7 cells……………………...79
Figure 23. Carboxy-PTIO decreases the insulin-enhanced Tyr phosphorylation of insulin receptor in eNOS-transfected COS-7 cells……….…...……80
Figure 24. The reduced forms of endogenous PTPs are decreased under insulin stimulation in eNOS-transfected COS-7 cells………………….…..81
Figure 25. Insulin stimulation causes the reversible inactivation of endogenous PTPs in eNOS-traansfected COS-7 cells………………………..…82
Figure 26. The NO-enhanced insulin signaling is mediated by the inactivation of PTPs………………………………………...………………….83
Figure 27. NO enhances phosphorylation of IRS-1 and PKB/Akt in signaling response to physiological levels of insulin…………………………84
Figure 28. The phosphorylation level of PKB/Akt is enhanced in COS-7 cells ectopically expressing low levels of eNOS…………………………85
Figure 29. The protein level of eNOS in endothelial MS-1 cells and eNOS-transfected COS-7 cells……………………..……………..86
Figure 30. Ablation of eNOS by RNAi suppresses insulin-induced activation of insulin receptor, IRS-1, and PKB in endothelial MS-1 cells………...87
Figure 31. The model illustrating the NO-mediated inactivation of protein tyrosine phosphatases enhances the insulin responsiveness…………….…...88

CHAPTER 6: REFERENCES………………………...…...……………...89

APPENDIX………....…………………...…………………………...….106
The manuscript published on-line in the Journal of Biological Chemistry
1.Neel, B.G. and N.K. Tonks, Protein tyrosine phosphatases in signal transduction. Curr Opin Cell Biol, 1997. 9(2): p. 193-204.
2.Hunter, T., Signaling--2000 and beyond. Cell, 2000. 100(1): p. 113-27.
3.Schlessinger, J., Cell signaling by receptor tyrosine kinases. Cell, 2000. 103(2): p. 211-25.
4.Pawson, T., G.D. Gish, and P. Nash, SH2 domains, interaction modules and cellular wiring. Trends Cell Biol, 2001. 11(12): p. 504-11.
5.Hubbard, S.R., Juxtamembrane autoinhibition in receptor tyrosine kinases. Nat Rev Mol Cell Biol, 2004. 5(6): p. 464-71.
6.Tonks, N.K., C.D. Diltz, and E.H. Fischer, Purification of the major protein-tyrosine-phosphatases of human placenta. J Biol Chem, 1988. 263(14): p. 6722-30.
7.Tonks, N.K., C.D. Diltz, and E.H. Fischer, Characterization of the major protein-tyrosine-phosphatases of human placenta. J Biol Chem, 1988. 263(14): p. 6731-7.
8.Charbonneau, H., et al., Human placenta protein-tyrosine-phosphatase: amino acid sequence and relationship to a family of receptor-like proteins. Proc Natl Acad Sci U S A, 1989. 86(14): p. 5252-6.
9.Charbonneau, H., et al., The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase. Proc Natl Acad Sci U S A, 1988. 85(19): p. 7182-6.
10.Ramponi, G. and M. Stefani, Structural, catalytic, and functional properties of low M(r), phosphotyrosine protein phosphatases. Evidence of a long evolutionary history. Int J Biochem Cell Biol, 1997. 29(2): p. 279-92.
11.Keyse, S.M., Protein phosphatases and the regulation of mitogen-activated protein kinase signalling. Curr Opin Cell Biol, 2000. 12(2): p. 186-92.
12.Andersen, J.N., et al., Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol Cell Biol, 2001. 21(21): p. 7117-36.
13.Andersen, J.N., et al., A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage. FASEB J, 2004. 18(1): p. 8-30.
14.Alonso, A., et al., Protein tyrosine phosphatases in the human genome. Cell, 2004. 117(6): p. 699-711.
15.Li, X., et al., Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature, 2003. 426(6964): p. 247-54.
16.Rayapureddi, J.P., et al., Eyes absent represents a class of protein tyrosine phosphatases. Nature, 2003. 426(6964): p. 295-8.
17.Tootle, T.L., et al., The transcription factor Eyes absent is a protein tyrosine phosphatase. Nature, 2003. 426(6964): p. 299-302.
18.Guan, K.L. and J.E. Dixon, Evidence for protein-tyrosine-phosphatase catalysis proceeding via a cysteine-phosphate intermediate. J Biol Chem, 1991. 266(26): p. 17026-30.
19.Barford, D., A.J. Flint, and N.K. Tonks, Crystal structure of human protein tyrosine phosphatase 1B. Science, 1994. 263(5152): p. 1397-404.
20.Su, X.D., et al., The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase. Nature, 1994. 370(6490): p. 575-8.
21.Yuvaniyama, J., et al., Crystal structure of the dual specificity protein phosphatase VHR. Science, 1996. 272(5266): p. 1328-31.
22.Fauman, E.B., et al., Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell, 1998. 93(4): p. 617-25.
23.Tonks, N.K., Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol, 2006. 7(11): p. 833-46.
24.Zhang, Z.Y. and J.E. Dixon, Active site labeling of the Yersinia protein tyrosine phosphatase: the determination of the pKa of the active site cysteine and the function of the conserved histidine 402. Biochemistry, 1993. 32(36): p. 9340-5.
25.Peters, G.H., T.M. Frimurer, and O.H. Olsen, Electrostatic evaluation of the signature motif (H/V)CX5R(S/T) in protein-tyrosine phosphatases. Biochemistry, 1998. 37(16): p. 5383-93.
26.Denu, J.M. and J.E. Dixon, Protein tyrosine phosphatases: mechanisms of catalysis and regulation. Curr Opin Chem Biol, 1998. 2(5): p. 633-41.
27.Rhee, S.G., et al., Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE, 2000. 2000(53): p. pe1.
28.Sundaresan, M., et al., Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science, 1995. 270(5234): p. 296-9.
29.Bae, Y.S., et al., Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J Biol Chem, 1997. 272(1): p. 217-21.
30.den Hertog, J., A. Groen, and T. van der Wijk, Redox regulation of protein-tyrosine phosphatases. Arch Biochem Biophys, 2005. 434(1): p. 11-5.
31.Salmeen, A. and D. Barford, Functions and mechanisms of redox regulation of cysteine-based phosphatases. Antioxid Redox Signal, 2005. 7(5-6): p. 560-77.
32.Tonks, N.K., Redox redux: revisiting PTPs and the control of cell signaling. Cell, 2005. 121(5): p. 667-70.
33.Babior, B.M., The leukocyte NADPH oxidase. Isr Med Assoc J, 2002. 4(11): p. 1023-4.
34.May, J.M. and C. de Haen, Insulin-stimulated intracellular hydrogen peroxide production in rat epididymal fat cells. J Biol Chem, 1979. 254(7): p. 2214-20.
35.Lambeth, J.D., NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol, 2004. 4(3): p. 181-9.
36.Denu, J.M. and K.G. Tanner, Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry, 1998. 37(16): p. 5633-42.
37.Lee, S.R., et al., Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J Biol Chem, 1998. 273(25): p. 15366-72.
38.Mahadev, K., et al., Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J Biol Chem, 2001. 276(24): p. 21938-42.
39.Meng, T.C., T. Fukada, and N.K. Tonks, Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell, 2002. 9(2): p. 387-99.
40.Meng, T.C., et al., Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B. J Biol Chem, 2004. 279(36): p. 37716-25.
41.Singh, D.K., et al., The strength of receptor signaling is centrally controlled through a cooperative loop between Ca2+ and an oxidant signal. Cell, 2005. 121(2): p. 281-93.
42.Kamata, H., et al., Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell, 2005. 120(5): p. 649-61.
43.Nimnual, A.S., L.J. Taylor, and D. Bar-Sagi, Redox-dependent downregulation of Rho by Rac. Nat Cell Biol, 2003. 5(3): p. 236-41.
44.Chiarugi, P., et al., Reactive oxygen species as essential mediators of cell adhesion: the oxidative inhibition of a FAK tyrosine phosphatase is required for cell adhesion. J Cell Biol, 2003. 161(5): p. 933-44.
45.Wu, R.F., et al., Subcellular targeting of oxidants during endothelial cell migration. J Cell Biol, 2005. 171(5): p. 893-904.
46.Stoker, A.W., Protein tyrosine phosphatases and signalling. J Endocrinol, 2005. 185(1): p. 19-33.
47.Saltiel, A.R., New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell, 2001. 104(4): p. 517-29.
48.Cheng, A., et al., Coordinated action of protein tyrosine phosphatases in insulin signal transduction. Eur J Biochem, 2002. 269(4): p. 1050-9.
49.Moller, N.P., et al., Selective down-regulation of the insulin receptor signal by protein-tyrosine phosphatases alpha and epsilon. J Biol Chem, 1995. 270(39): p. 23126-31.
50.Kulas, D.T., et al., Insulin receptor signaling is augmented by antisense inhibition of the protein tyrosine phosphatase LAR. J Biol Chem, 1995. 270(6): p. 2435-8.
51.Ren, J.M., et al., Transgenic mice deficient in the LAR protein-tyrosine phosphatase exhibit profound defects in glucose homeostasis. Diabetes, 1998. 47(3): p. 493-7.
52.Zabolotny, J.M., et al., Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance. Proc Natl Acad Sci U S A, 2001. 98(9): p. 5187-92.
53.Ahmad, F., et al., Osmotic loading of neutralizing antibodies demonstrates a role for protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway. J Biol Chem, 1995. 270(35): p. 20503-8.
54.Kenner, K.A., et al., Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signaling. J Biol Chem, 1996. 271(33): p. 19810-6.
55.Salmeen, A., et al., Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol Cell, 2000. 6(6): p. 1401-12.
56.Walchli, S., et al., Identification of tyrosine phosphatases that dephosphorylate the insulin receptor. A brute force approach based on "substrate-trapping" mutants. J Biol Chem, 2000. 275(13): p. 9792-6.
57.Galic, S., et al., Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. Mol Cell Biol, 2003. 23(6): p. 2096-108.
58.Dubois, M.J., et al., The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nat Med, 2006. 12(5): p. 549-56.
59.Myers, M.G., Jr., et al., The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling. J Biol Chem, 1998. 273(41): p. 26908-14.
60.Tsui, H.W., et al., Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet, 1993. 4(2): p. 124-9.
61.Majeti, R., et al., An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell, 2000. 103(7): p. 1059-70.
62.Hasegawa, K., et al., PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells. Science, 2004. 303(5658): p. 685-9.
63.Tchilian, E.Z., et al., A deletion in the gene encoding the CD45 antigen in a patient with SCID. J Immunol, 2001. 166(2): p. 1308-13.
64.Jury, E.C., et al., Altered lipid raft-associated signaling and ganglioside expression in T lymphocytes from patients with systemic lupus erythematosus. J Clin Invest, 2004. 113(8): p. 1176-87.
65.Begovich, A.B., et al., A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet, 2004. 75(2): p. 330-7.
66.Kyogoku, C., et al., Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet, 2004. 75(3): p. 504-7.
67.Ostman, A., C. Hellberg, and F.D. Bohmer, Protein-tyrosine phosphatases and cancer. Nat Rev Cancer, 2006. 6(4): p. 307-20.
68.Wang, Z., et al., Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science, 2004. 304(5674): p. 1164-6.
69.Ruivenkamp, C.A., et al., Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers. Nat Genet, 2002. 31(3): p. 295-300.
70.Ruivenkamp, C., et al., LOH of PTPRJ occurs early in colorectal cancer and is associated with chromosomal loss of 18q12-21. Oncogene, 2003. 22(22): p. 3472-4.
71.Iuliano, R., et al., The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis. Oncogene, 2004. 23(52): p. 8432-8.
72.Zhang, Q., et al., Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter. Am J Pathol, 2000. 157(4): p. 1137-46.
73.Oka, T., et al., Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas. Cancer Res, 2002. 62(22): p. 6390-4.
74.Kim, J.R., et al., Identification of proteins containing cysteine residues that are sensitive to oxidation by hydrogen peroxide at neutral pH. Anal Biochem, 2000. 283(2): p. 214-21.
75.Weibrecht, I., et al., Oxidation sensitivity of the catalytic cysteine of the protein-tyrosine phosphatases SHP-1 and SHP-2. Free Radic Biol Med, 2007. 43(1): p. 100-10.
76.Wu, Y., K.S. Kwon, and S.G. Rhee, Probing cellular protein targets of H2O2 with fluorescein-conjugated iodoacetamide and antibodies to fluorescein. FEBS Lett, 1998. 440(1-2): p. 111-5.
77.Krishnamurthy, D. and A.M. Barrios, Profiling protein tyrosine phosphatase activity with mechanistic probes. Curr Opin Chem Biol, 2009. 13(4): p. 375-81.
78.Lo, L.C., et al., Design and synthesis of class-selective activity probes for protein tyrosine phosphatases. J Proteome Res, 2002. 1(1): p. 35-40.
79.Kumar, S., et al., Activity-based probes for protein tyrosine phosphatases. Proc Natl Acad Sci U S A, 2004. 101(21): p. 7943-8.
80.Liu, S., et al., Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases. J Am Chem Soc, 2008. 130(26): p. 8251-60.
81.Lane, P., G. Hao, and S.S. Gross, S-nitrosylation is emerging as a specific and fundamental posttranslational protein modification: head-to-head comparison with O-phosphorylation. Sci STKE, 2001. 2001(86): p. re1.
82.Stuart-Smith, K., Demystified. Nitric oxide. Mol Pathol, 2002. 55(6): p. 360-6.
83.Palmer, R.M., et al., L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun, 1988. 153(3): p. 1251-6.
84.Palmer, R.M., D.S. Ashton, and S. Moncada, Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature, 1988. 333(6174): p. 664-6.
85.Palmer, R.M. and S. Moncada, A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun, 1989. 158(1): p. 348-52.
86.Fleming, I. and R. Busse, NO: the primary EDRF. J Mol Cell Cardiol, 1999. 31(1): p. 5-14.
87.Dudzinski, D.M. and T. Michel, Life history of eNOS: partners and pathways. Cardiovasc Res, 2007. 75(2): p. 247-60.
88.Mount, P.F., B.E. Kemp, and D.A. Power, Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation. J Mol Cell Cardiol, 2007. 42(2): p. 271-9.
89.Howlett, R., Nobel award stirs up debate on nitric oxide breakthrough. Nature, 1998. 395(6703): p. 625-6.
90.Feil, R. and B. Kemp-Harper, cGMP signalling: from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications. EMBO Rep, 2006. 7(2): p. 149-53.
91.Stone, J.R. and M.A. Marletta, Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry, 1994. 33(18): p. 5636-40.
92.Mayer, B., Nitric oxide/cyclic GMP-mediated signal transduction. Ann N Y Acad Sci, 1994. 733: p. 357-64.
93.Myers, P.R., et al., Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature, 1990. 345(6271): p. 161-3.
94.Stamler, J., et al., N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor. Circ Res, 1989. 65(3): p. 789-95.
95.Stamler, J.S., et al., Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci U S A, 1992. 89(16): p. 7674-7.
96.Stamler, J.S., et al., S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A, 1992. 89(1): p. 444-8.
97.Miersch, S. and B. Mutus, Protein S-nitrosation: biochemistry and characterization of protein thiol-NO interactions as cellular signals. Clin Biochem, 2005. 38(9): p. 777-91.
98.Jaffrey, S.R., et al., Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol, 2001. 3(2): p. 193-7.
99.Stamler, J.S., S. Lamas, and F.C. Fang, Nitrosylation. the prototypic redox-based signaling mechanism. Cell, 2001. 106(6): p. 675-83.
100.Kuncewicz, T., et al., Proteomic analysis of S-nitrosylated proteins in mesangial cells. Mol Cell Proteomics, 2003. 2(3): p. 156-63.
101.Nathan, C. and Q.W. Xie, Nitric oxide synthases: roles, tolls, and controls. Cell, 1994. 78(6): p. 915-8.
102.Schmidt, H.H. and U. Walter, NO at work. Cell, 1994. 78(6): p. 919-25.
103.Gow, A.J., et al., Basal and stimulated protein S-nitrosylation in multiple cell types and tissues. J Biol Chem, 2002. 277(12): p. 9637-40.
104.Hess, D.T., et al., Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol, 2005. 6(2): p. 150-66.
105.Hoffmann, J., S. Dimmeler, and J. Haendeler, Shear stress increases the amount of S-nitrosylated molecules in endothelial cells: important role for signal transduction. FEBS Lett, 2003. 551(1-3): p. 153-8.
106.Matsushita, K., et al., Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell, 2003. 115(2): p. 139-50.
107.Garban, H.J., et al., Rapid nitric oxide-mediated S-nitrosylation of estrogen receptor: regulation of estrogen-dependent gene transcription. Proc Natl Acad Sci U S A, 2005. 102(7): p. 2632-6.
108.Levine, R., M. Goldstein, and et al., The action of insulin on the distribution of galactose in eviscerated nephrectomized dogs. J Biol Chem, 1949. 179(2): p. 985.
109.Cohen, P., The twentieth century struggle to decipher insulin signalling. Nat Rev Mol Cell Biol, 2006. 7(11): p. 867-73.
110.Kasuga, M., F.A. Karlsson, and C.R. Kahn, Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science, 1982. 215(4529): p. 185-7.
111.Petruzzelli, L.M., et al., Insulin activates a tyrosine-specific protein kinase in extracts of 3T3-L1 adipocytes and human placenta. Proc Natl Acad Sci U S A, 1982. 79(22): p. 6792-6.
112.Muniyappa, R., et al., Cardiovascular actions of insulin. Endocr Rev, 2007. 28(5): p. 463-91.
113.Zeng, G. and M.J. Quon, Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest, 1996. 98(4): p. 894-8.
114.Zeng, G., et al., Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation, 2000. 101(13): p. 1539-45.
115.Montagnani, M., et al., Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem, 2001. 276(32): p. 30392-8.
116.Montagnani, M., et al., Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol Endocrinol, 2002. 16(8): p. 1931-42.
117.Baron, A.D., et al., Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats. Am J Physiol, 1995. 269(4 Pt 1): p. E709-15.
118.Roy, D., M. Perreault, and A. Marette, Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent. Am J Physiol, 1998. 274(4 Pt 1): p. E692-9.
119.Balon, T.W. and J.L. Nadler, Evidence that nitric oxide increases glucose transport in skeletal muscle. J Appl Physiol, 1997. 82(1): p. 359-63.
120.Young, M.E., G.K. Radda, and B. Leighton, Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro. Biochem J, 1997. 322 ( Pt 1): p. 223-8.
121.Higaki, Y., et al., Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. Diabetes, 2001. 50(2): p. 241-7.
122.Shankar, R.R., et al., Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance. Diabetes, 2000. 49(5): p. 684-7.
123.Duplain, H., et al., Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation, 2001. 104(3): p. 342-5.
124.Cook, S., et al., Partial gene deletion of endothelial nitric oxide synthase predisposes to exaggerated high-fat diet-induced insulin resistance and arterial hypertension. Diabetes, 2004. 53(8): p. 2067-72.
125.Kapur, S., et al., Expression of nitric oxide synthase in skeletal muscle: a novel role for nitric oxide as a modulator of insulin action. Diabetes, 1997. 46(11): p. 1691-700.
126.Engeli, S., et al., Regulation of the nitric oxide system in human adipose tissue. J Lipid Res, 2004. 45(9): p. 1640-8.
127.Galic, S., et al., Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol Cell Biol, 2005. 25(2): p. 819-29.
128.Caselli, A., et al., Nitric oxide causes inactivation of the low molecular weight phosphotyrosine protein phosphatase. J Biol Chem, 1994. 269(40): p. 24878-82.
129.Caselli, A., et al., In vivo inactivation of phosphotyrosine protein phosphatases by nitric oxide. FEBS Lett, 1995. 374(2): p. 249-52.
130.Takakura, K., et al., Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite. Arch Biochem Biophys, 1999. 369(2): p. 197-207.
131.Xian, M., et al., Inhibition of protein tyrosine phosphatases by low-molecular-weight S-nitrosothiols and S-nitrosylated human serum albumin. Biochem Biophys Res Commun, 2000. 268(2): p. 310-4.
132.Li, S. and A.R. Whorton, Regulation of protein tyrosine phosphatase 1B in intact cells by S-nitrosothiols. Arch Biochem Biophys, 2003. 410(2): p. 269-79.
133.Barrett, D.M., et al., Inhibition of protein-tyrosine phosphatases by mild oxidative stresses is dependent on S-nitrosylation. J Biol Chem, 2005. 280(15): p. 14453-61.
134.Yu, C.X., S. Li, and A.R. Whorton, Redox regulation of PTEN by S-nitrosothiols. Mol Pharmacol, 2005. 68(3): p. 847-54.
135.Chen, Y.Y., et al., Mass spectrometry-based analyses for identifying and characterizing S-nitrosylation of protein tyrosine phosphatases. Methods, 2007. 42(3): p. 243-9.
136.Chen, Y.Y., et al., Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation. J Biol Chem, 2008. 283(50): p. 35265-72.
137.Forrester, M.T., M.W. Foster, and J.S. Stamler, Assessment and application of the biotin switch technique for examining protein S-nitrosylation under conditions of pharmacologically induced oxidative stress. J Biol Chem, 2007. 282(19): p. 13977-83.
138.Burridge, K. and A. Nelson, An in-gel assay for protein tyrosine phosphatase activity: detection of widespread distribution in cells and tissues. Anal Biochem, 1995. 232(1): p. 56-64.
139.He, X.M. and D.C. Carter, Atomic structure and chemistry of human serum albumin. Nature, 1992. 358(6383): p. 209-15.
140.Peterson, M.D. and M.S. Mooseker, Characterization of the enterocyte-like brush border cytoskeleton of the C2BBe clones of the human intestinal cell line, Caco-2. J Cell Sci, 1992. 102 ( Pt 3): p. 581-600.
141.Dzierzewicz, Z., et al., Changes in the cellular behaviour of human colonic cell line Caco-2 in response to butyrate treatment. Acta Biochim Pol, 2002. 49(1): p. 211-20.
142.Ibarra-Sanchez, M.J., et al., Murine embryonic fibroblasts lacking TC-PTP display delayed G1 phase through defective NF-kappaB activation. Oncogene, 2001. 20(34): p. 4728-39.
143.Simoncic, P.D., et al., T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation. Mol Cell Biol, 2006. 26(11): p. 4149-60.
144.Iwakiri, Y., et al., Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. Proc Natl Acad Sci U S A, 2006. 103(52): p. 19777-82.
145.Elchebly, M., et al., Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science, 1999. 283(5407): p. 1544-8.
146.Ouwens, D.M., G.C. van der Zon, and J.A. Maassen, Modulation of insulin-stimulated glycogen synthesis by Src Homology Phosphatase 2. Mol Cell Endocrinol, 2001. 175(1-2): p. 131-40.
147.Whiteman, E.L., H. Cho, and M.J. Birnbaum, Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab, 2002. 13(10): p. 444-51.
148.Gonzalez, E. and T.E. McGraw, Insulin signaling diverges into Akt-dependent and -independent signals to regulate the recruitment/docking and the fusion of GLUT4 vesicles to the plasma membrane. Mol Biol Cell, 2006. 17(10): p. 4484-93.
149.Hao, G., et al., SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites in complex protein mixtures. Proc Natl Acad Sci U S A, 2006. 103(4): p. 1012-7.
150.Greco, T.M., et al., Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells. Proc Natl Acad Sci U S A, 2006. 103(19): p. 7420-5.
151.Di Guglielmo, G.M., et al., Insulin receptor internalization and signalling. Mol Cell Biochem, 1998. 182(1-2): p. 59-63.
152.Lorenzen, J.A., C.Y. Dadabay, and E.H. Fischer, COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol, 1995. 131(3): p. 631-43.
153.Tiganis, T., et al., Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. Mol Cell Biol, 1998. 18(3): p. 1622-34.
154.Blanchetot, C., et al., Substrate-trapping techniques in the identification of cellular PTP targets. Methods, 2005. 35(1): p. 44-53.
155.Sambuy, Y., et al., The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol, 2005. 21(1): p. 1-26.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊