Phosphotyrosine phosphatase SHP-1, somatostatin and prostate cancer;Fosfotirosina fosfatasa SHP-1, somatostatina y cáncer de próstata

Actas Urologicas Espanolas

Volumn 28, Issue 4, 2004, Pages 269-285

  Zapata, P D ^a   Colas, B ^a   Lopez Ruiz P ^a   Ropero, R M ^a   Martin R M ^a   Rodriguez F J ^a   Gonzalez F J ^a   Lopez J I ^a   Angulo Javier C , J C ^a  

^a UNIVERSITY OF ALCALÁ   (Spain)

Author keywords

Neuroendocrine cell; Prostate; Prostate neoplasm; Protein tyrosin phosphatase; SHP 1; Somatostatin

Indexed keywords

PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE SHP 1; PTPN6 PROTEIN, HUMAN; SIGNAL PEPTIDE; SOMATOSTATIN;

CELL DIVISION; CYTOLOGY; DISEASE COURSE; FORECASTING; GROWTH, DEVELOPMENT AND AGING; HUMAN; MALE; MEDICAL RESEARCH; NEUROSECRETION; PATHOLOGY; PHYSIOLOGY; PROSTATE; PROSTATE TUMOR; REVIEW;

BIOMEDICAL RESEARCH; CELL DIVISION; DISEASE PROGRESSION; FORECASTING; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; NEUROSECRETORY SYSTEMS; PROSTATE; PROSTATIC NEOPLASMS; PROTEIN-TYROSINE-PHOSPHATASE; SHP1 PROTEIN TYROSINE PHOSPHATASE; SOMATOSTATIN;

EID: 4644278989     PISSN: 02104806     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0210-4806(04)73075-2     Document Type: Review

References (101)

1. DENIS LJ.: Maximal androgen blockade: facts and fallacies. Endocr Rel Cancer 1998; 5: 353-356.
2. GRIFFITHS K.: Molecular control of prostate growth. In textbook of benign prostatic hyperplasia, 1 edn. Edited by Kirby R, Mc Connell JD, Fitzpatrick JM, Roehrborn CG, Boyle P. Oxford (UK): Isis Medical Media 1996: 23-55.
3. RUIJTER E, VAN DE KAA C, MILLER G. RUITER D, DEBRUYNE F, SCHALKEN J.: Molecular genetics and epidemiology of prostate cancer. Endoc Rev 1999; 20: 22-45.
4. RUSSELL DW, WILSON JD.: Steroid 5α reductase: two genes/two enzymes. Rew Biochem 1994; 63: 25.
5. JENSTER G.: The role of the androgen receptor in the development and progression of prostate cancer. Semin Oncol 1999; 26: 407-421.
6. BERTHON P, WALLER AS, VILLETTE JM.: Androgen are not a direct requirement for the proliferation of human prostatic epithelium in vitro. Int J Cancer 1997; 73: 910-916.
7. BYRNE RL, LEUNG H, NEAL DE.: Peptide growth factors in the prostate as mediators of stromal epithelial interactions. Br J Urol 1996; 77: 627-633.
8. RUSSELL P, BENNETT S, STRICKER P.: Growth factor involvement in progression of prostate cancer. Clin Chem 1998; 44: 705-723.
9. DJAKIEW D.: Dysregulated expression of growth factors and their receptors in the development of prostate cancer. Prostate 2000; 42: 150-160.
10. ABRAHAMSSON PA.: Neuroendocrine differentiation in prostatic carcinoma. Prostate 1999; 39: 135-148.
11. APRIKIAN A, HAN K, GUY L, LANDRY F, BEGIN L, CHEVALIER S.: Neuroendocrine differentiation and the bombesin/gastrin-releasing peptide family of neuropeptides in the progression of human prostate cancer. Prostate Suppl 1998; 8: 52-61.
12. JIBORN T, BJARTELL A, ABRAHAMSSON PA.: Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology 1998; 51: 585-589.
13. BONKHOFF H.: Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status. Prostate 1998; 8: 18-22.
14. DI SANTAGNESE PA.: Neuroendocrine differentiation in prostatic carcinoma. Hum Pathol 1992; 23: 287-296.
15. PATEL YC.: General aspects of the biology and function of somatostatin. In Basic and clinical aspects of neuroscience, 1992 edn. Edited by Weil C, Muller EE, Thorner MO. Berlin: Springer-Verlag 1992: 1-16.
16. POLLAK MN, SCHALLY AV.: Mechanisms of antineoplastic action somatostatin analogs. Proc Soc Exp Biol Med 1998; 217: 1431-1452.
17. LAMBERTS SWJ, KRENNING EP, REUBI JC.: The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocrine Rev 1991; 12: 450-482.
18. YAMADA Y, POST SR, WANG K et al.: Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci USA 1992; 89: 251-255.
19. PATEL YC.: Somatostatin and its receptor family. Front Neuroendocrinol 1999; 20: 157-198.
20. WECKBECKER G, RAULF F, BODMER D, BRUNS C.: Indirect antiproliferative effect of the somatostatin analog octreotide on MIA PaCa-2 human pancreatic carcinoma in nude mice. Yale J Biol Med 1998; 70: 549-554.
21. LAMBERTS SW, VAN DER LELY A, DEHARDER WW, HOFLAND LJ.: Drug therapy: octreotide. New Eng J Med 1996; 334: 246-254.
22. FIGG WD, THIBAULT A, COOPER MR et al.: A phase I study of the somatostatin analogue somatuline in patients with metastatic hormone refractory prostate cancer. Cancer 1995; 15: 2159-2164.
23. MAULARD C, RICHAUD P, DROZ JP, JESSUELD D, DUFOUR-ESQUERRE F, HOUSSET M.: Phase I-II study of the somatostatin analogue lanreotide in hormone-refactory prostate cancer. Cancer Chemother Pharmacol 1995; 36: 259-262.
24. LOGOTHETIS CJ, HOSSAN EA, SMITH TL.: SMS 201-995 in the treatment of refractory prostatic carcinoma. Anticancer Res 1994; 14: 2731-2734.
25. BUSCAIL L, DELESQUE N, ESTEVE JP et al.: Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SST1 and SST2. Proc Natl Acad Sci USA 1994; 91: 2315-2319.
26. PATEL YC, GREENWOOD MT, KENT G, PANETTA R, SRIKANT CB.: Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. Biochem Biophys Res Commun 1993; 192: 288-294.
27. BUSCAIL L, SAINT-LAURENT N, CHASTRE E et al.: Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer. Cancer Res 1996; 56: 1823-1827.
28. ROCHAIX P, DELESQUE N, ESTEVE JP et al.: Gene therapy for pancreatic carcinoma: local and distant antitumor effects after somatostatin receptor sst2 gene transfer. Hum Gene Ther 1999; 10: 995-1008.
29. DELESQUE N, BUSCAIL L, ESTEVE JP et al.: sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells. Cancer Res 1997; 57: 956-962.
30. TONKS NK, CHARBONNEAU H.: Protein tyrosine dephosphorylation and signal transduction. TIBS 1989: 14: 497-500.
31. FAUMAN EB, SAPER MA.: Structure and function of the protein tyrosine phosphatases. TIBS 1996; 21: 413-417.
32. TONKS NK, NEEL BG.: Combinatorial control of the specificity of protein tyrosine phosphatases. Curr Opin Cell Biol 2001; 13: 182-195.
33. SUN H, TONKS NK.: The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. TIBS 1994; 19: 480-485.
34. KEYSE S.M.: Protein phosphatases and the regulation of mitogen activated protein kinase signaling. Curr Opin Cell Biol 2000; 12: 186-192.
35. WISHART MJ, TAYLOR GS, SLAMA JT, DIXON JE.: PTEN and myotubularion phosphoinositide phosphatases: bringing bioinformatics to the lab bench. Curr Opin Cell Biol 2001; 13: 172-181.
36. BLONDEAU F, LAPORTE J, BODIN S, SUPERTIFURGA G, PAYRASTRE B, MANDEL J.: Myorubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. Hum Mol Genet 2000; 9: 2223-2229.
37. SADOWSKI Y, STONE JC, PAWSON T.: A non catalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130 gag-fps. Mol Cell Biol 1986; 6: 4396-4408.
38. SHEN S, BASTIEN L, POSNER BI, CHRETIEN P.: A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature 1991; 352: 736-739.
39. PLUTZKY J, NEEL BG, ROSENBERG RD.: Isolation of a src homology 2-containing tyrosine phosphatase. Proc atl Acad Sci USA 1992; 89: 1123-1127.
40. MATTHEWS RJ, BOWNE DB, FLORES E, THOMAS ML.: Characterization of hematopoietic, intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Biol 1992; 12: 2396-2405.
41. VOGEL W, LAMMERS R, HUANG J, ULLRICH A.: Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science 1993; 259: 1611-1614.
42. AHMAN S, BANVILLE D, ZHAO Z, FISCHER EH, SHEN SH.: A widely expressed human protein tyrosine phosphatase containing src homology 2 domains. Proc Natl Acad USA 1994; 90: 2197-2201.
43. FREEMAN JRRM, PLUTZKY J, NEEL BG.: Identification of a human src homology 2-containing protein tyrosine-phosphatase. Proc Natl Acad Sci USA 1992; 89: 11239-11243.
44. FENG GS, HUI CC, PAWSON T.: SH2-containing phosphotyrosine phosphatase as a target of protein tyrosine kinase. Science 1993; 259: 1607-1611.
45. ADACHI M, SEKIYA M, MIYACHI T et al,: Molecular cloning and sequencing of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology 2 region. FEBS Let 1993; 314: 335-339.
46. MATOZAK1 T, UCHIDA T, FUJIOKA Y, KASUGA M.: Src kinase tyrosine phosphorylates PTP1C, a protein tyrosine phosphatase containing Src homology-2 domains that down-regulates cell proliferation. Biochem Biophys Res Commun 1994; 204: 871-881.
47. MATOZAKI T, KASUGA M.: Roles of protein-tyrosine phosphatases in growth factor signaling. Cell Signal 1996; 8: 13-19.
48. BANVILLE D, STOCCO R, SHEN SH.: Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate promoter usage and exon skipping generate multiple transcripts. Genomics 1995; 27: 165-173.
49. SHULTZ LD, GREEN MC.: Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. J Immunol 1976; 116: 936-943.
50. SHULTZ LD, RAJAN TV, GREINER DL.: Severe defects in immunity and hematopoietic caused by SHP-1 protein-tyrosine phosphatase deficiency. Trends Biotechnol 1997; 15: 302-307.
51. SCHWARTZ MA, BARON V.: Interactions between mitogenic stimuli, or, a thousand and one connections. Curr Opin Cell Biol 1999; 11: 197-202.
52. TOMIC S, GREISER U, LAMMERS R et al.: Association of SH2 domain protein tyrosine phosphatases with the epidermal growth factor receptor in human tumor cells. Phosphatidic acid activates receptor dephosphorylation by PTP1C. J Biol Chem 1995; 270: 21277-21284.
53. TENEV T. KEILHACK H, TOMIC S et al.: Both SH2 domain are involved in interaction of SHP-1 with the epidermal growth factor receptor but cannot confer receptor-directed activity to SHP-1/SHP-1 chimera. J Biol Chem 1997; 272: 5966-5973.
54. VAMBUTAS V, KAPLAN DR, SELLS MA, CHERNOFF J.: Nerve growth factor stimulates tyrosine phosphorylation and activation of Src homology-containing protein-tyrosine phosphatase 1 in PC 12 cells. J Biol Chem 1995; 270: 25629-25633.
55. 538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains. J Biol Chem 1994; 269: 12220-12228.
56. MACHIDE M, KAMITORI K. KOHSAKA S.: Hepatocyte growth factor-induced differential activation of phospholipase Cγ1 and phosphatidylinositol 3-kinase is regulated by tyrosine phosphatase SHP-1 in astrocytes. J Biol Chem 2000; 275: 31392-31398.
57. YI T, MUI ALF, KRISTAL G, IHLE JN.: Hematopoietic cell phosphatase associates with the interleukin-3 (IL-3) receptor b chain and down-regulates IL-3 -induced tyrosine phosphorylation and mitogenesis. Mol Cell Biol 1993; 13: 7577-7585.
58. KLINGMÜLLER U, LORENZ U, CANTLEY LC, NEEL BG, LODISH HF.: Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell 1995; 80: 729-738.
59. DAVID M, CHEN HE, LING L, GOELZ S, LARNER AC, NEEL BG.: Differential regulation of the a/b interferon-stimulated Jak/Stat pathway by the SH2-domain containing tyrosine phosphatase SHPTP1. Mol Cell Biol 1995; 15: 7050-7058.
60. JIAO H, BERRADA K, YANG W, TABRIZI M, PLATANIAS LC, YI T.: Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1. Mol Cell Biol 1996; 16: 6985-6992.
61. BEDECS K, ELBAZ N, SUTREN M et al.: Angiotensin II type 2 mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. Biochem J 1997; 325: 449-454.
62. LÓPEZ F, ESTEVE JP, BUSCAIL L y cols.: The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. J Biol Chem 1997; 272: 24448-24454.
63. ZAPATA P, ROPERO RM, VALENCIA AM y cols.: Autocrine regulation of PC3 prostate cell proliferation by somatostatin through the modulation of SHP-1. J Clin Endocrinol Metabolism 2002; 87: 915-926.
64. SU L, ZHAO ZJ, BOUCHARD P, BANVILLE D, FISCHER EH, KREBS EG, SHEN S.: Positive effect of overexpressed protein-tyrosine phosphatase PTP1C on mitogen-activated signaling in 293 cells. J Biol Chem 1996; 271: 10385-10390.
65. FLORIO T, YAO H, CAREY KD, DILLON TJ, STORK PJS.: Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). Mol Endoc 1999: 13: 24-37.
66. 1 cell cycle arrest. Mol Endoc 1999; 13: 82-90.
67. REARDON DB, DENT P, WOOD SL, KONG T, STURGILL TW.: Activation in vitro of somatostatin receptor subtypes 2, 3, or 4 stimulates protein tyrosine phosphatase activity in membranes from transfected ras- transformed NIH 3T3 cells: coexpression with catalitically inactive SHP-2 blocks responsiveness. Mol Endoc 1997; 11: 1062-1069.
68. ZEGGARI M, ESTEVE JP, RAULY I y cols.: Co-purification of a protein tyrosine phosphatase with activated somatostatin receptors from rat pancreatic acinar membranes, Biochem J 1994; 303: 441-448.
69. BOUSQUET C, DELESQUE N, LÓPEZ F y cols.: sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1, J Biol Chem 1998; 273: 7099-7106.
70. RAULY I, SAINT-LAURENT N, DELESQUE N y cols.: Induction of a negative autocrine loop by expression of sst2 somatostatin receptor in NIH 3T3 cells. J Clin Invest 1996; 97: 1874-1883.
71. Kip1. J Biol Chem 1999; 274: 15186-15193.
72. LÓPEZ, F, FERJOUX G, CORDELIER P y cols.: Neuronal nitric oxide synthase is a SHP-1 substrate involved in sst2 somatostatin receptor growth inhibitory signaling. FASEB J 2001.
73. kip1. Endocrinology 1999; 140: 87-95.
74. 1-S transition mediated by cAMP-dependent protein kinase and phosphatidylinositol 3-kinase. J Biol Chem 2000; 275: 15549-15556.
75. SRIKANT CB, SHEN S.: Octapeptide somatostatin analog SMS 201-995 induces translocation of intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells. Endocrinology 1996; 137: 3461-3468.
76. SHARMA K, PATEL YC, SRIKANT CB.: Subtype selective induction of wild type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endoc 1996; 10: 1688-1696.
77. SHARMA K, SRIKANT CB.: Induction of wild-type p53, Bax, and acid endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer cells. Int J Cancer 1998; 76: 259-266.
78. LIU D, MARTINO G, THANGARAJU M y cols.: Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis. J Biol Chem 2000; 275: 9244-9250.
79. SHARMA K, SRIKANT CB.: G protein coupled receptor signaled apoptosis is associated with activation of a cation insensitive acidic endonuclease and intracellular acidification. Biochem Biophys Res Commun 1998; 242: 134-140.
80. THANGARAJU M, SHARMA K, LEBER B, ANDREWS DW, SHEN S, SRIKANT CB.: Regulation of acidification and apoptosis by SHP-1 and Bcl-2. J Biol Chem 1999; 274: 29549-29557.
81. THANGARAJU M, SHARMA K, LIU D, SHEN SH, SRIKANT CB.: Interdependent regulation of intracellular acification and SHP-1 in apoptosis. Cancer Res 1999: 59: 1649-1654.
82. DI SANT'AGNESE PA, DE MESY JENSEN KL.: Somatostatin and/or somatostatin like immunoreactive endocrine-paracrine cells in the human prostate gland. Arch Pathol Lab Med 1984; 108: 693-696.
83. PINSKI J, SCHALLY AV, HALMOS G, SZEPESHAZI K.: Effect of somatostatin analog RC-160 and bombesin/gastrin releasing peptide antagonist RC-3095 on growth of PC-3 human prostate cancer xenografts in nude mice. Int J Cancer 1993; 55: 963-967.
84. VERHELST J, DE LONGUEVILLE M, ONGENA P, DENIS L, MAHLER C.: Octreotide in advanced prostatic cancer relapsing under hormonal treatment. Acta Urol Belg 1994; 62: 83-88.
85. VAINAS G, PASAITOU V, GALAKTIDOU G y cols.: The role of somatostatin analogues incomplete antiandrogen treatment in patients with prostatic carcinoma. J Exp Clin Cancer Res 1997; 16: 119-126.
86. BERRUTI A, DOGLIOTTI L, MOSCA A y cols.: Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen and insulin-like growth factor-1 in advanced prostate cancer patients. Prostate 2001; 47: 205-211.
87. REUBI JC, WASER B, SCHAER J, MARKWALDER, R.: Somatostatin receptors in human prostate and prostate cancer. J Clin Endocrinol Metab 1995; 80: 2806-2814.
88. SUNISI AA, BELLASTELLA A, PREZIOSO D y cols.: Different expression patterns of somatostatin receptor subtypes in cultured epithelial cells from human normal prostate and prostate cancer. J Clin Endocrinol Metab 1997; 82: 2566-2569.
89. HALMOS G, SCHALLY AV, SUN B, DAVIS R, BOSTWICK DG, PLONOWSKI A.: High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers. J Clin Endocrinol Metab 2000; 85: 2564-2571.
90. BREVINI TA, BIANCHI R, MOTTA M.: Direct inhibitory effect of somatostatin on the growth of the human prostatic cancer cell line LNCaP: possible mechanism of action. J Clin Endocinol Metab 1993; 77: 626-631.
91. VALENCIA AM, OLIVA JL, ANGULO JC, PRIETO JC, COLÁS B.: Identification of PTP1C in prostate tumor cells. Regulation by EGF. 92nd Annual Meeting Amer. Urolog. Assoc., New Orleans, Louisiana (USA) 1997.
92. LÓPEZ JI, ANGULO J, COLÁS B y cols.: Identification of SHP-1 in the prostate and its possible implication in the development and progression of prostate cancer. 91st Annual Meeting of the United States and Canadian of Academy Pathology, Chicago, IL, february 23 to march 1, 2002.
93. ZAPATA P, ROPERO RM, LÓPEZ-RUIZ MP, LÓPEZ JI, ANGULO J, COLAS B.: Somatostatina y cáncer de próstata. Revisiones en Urología 2000; 1: 7-16.
94. VALENCIA AM, OLIVA JL, BODEGA G y cols.: Identification of a protein-tyrosine phosphatase (SHP1) different from that associated with acid phosphatase in rat prostate. FEBS Let 1997; 406: 42-48.
95. FLORIO T, THELLUNG S, ARENA S, CORSARO A, BAJETTO A, SCHETTINI G, STORK PJS.: Somatostatin receptor 1 (SSTR1)-mediated inhibition of cell proliferation correlates with the activation of the MAP kinase cascade: role of the phosphotyrosine phosphatase SHP-2. J Physiol 2000; 94: 239-250.
96. DOUZIECH N, CALVO E, COULOMBE Z et al.: Inhibitory and stimulatory effects of somatostatin on two human pancreatic cancer cell lines: a primary role for tyrosine phosphatase SHP-1. Endocrinology 1999; 140: 765-777.
97. KOSSEV PM, RAGHUNATH PN, BAGG A, SCHUSTER S, TOMASZEWSKI JE, WASIK NA.: SHP-1 expression by malignant small B-cell lymphomas reflects the maturation stage of their normal B-cell counterparts. Am J Surg Pathol 2001; 25: 949-955.
98. ZHANG J. SOMANI A-K, SIMINOVITCH KA.: Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signaling. Semin Immunol 2000; 12: 361-378.
99. DELIBRIAS CC, FLOETTMANN JE, ROWE M, FEARON DT.: Down regulated expression of SHP1 in Burkitt lymphomas and germinal center B lymphocytes. J Exp Med 1997; 186: 1575-1583.
100. WICKREMA A, CHEN F, NAMIN F, YI T et al.: Defective expression of SHP-1 phosphatase in polycythemia vera. Exp Hematol 1999; 27: 1124-1132.
101. BENALI N, CORDELIER P, CAUSE D, PAGÉS P, ROCHAIX P, NAGY A. ESTEVE JP, POUR PM, SCHALLY AV, VAYSSE N, SUSINI C, BUSCAIL L.: Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238. Proc Natl Acad Sci USA 2000: 97: 9180-9185.