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. 2000 Feb;32(2):109–123. doi: 10.1023/A:1008170710003

Advances in animal cell recombinant protein production: GS-NS0 expression system

Louise M Barnes 1,, Catherine M Bentley 2, Alan J Dickson 3
PMCID: PMC3449689  PMID: 19002973

Abstract

The production of recombinant proteins using mammalian cell expression systems is of growing importance within biotechnology, largely due to the ability of specific mammalian cells to carry out post-translational modifications of the correct fidelity. The Glutamine Synthetase-NS0 system is now one such industrially important expression system.Glutamine synthetase catalyses the formation ofglutamine from glutamate and ammonia. NS0 cellscontain extremely low levels of endogenous glutaminesynthetase activity, therefore exogenous glutaminesynthetase can be used efficiently as a selectablemarker to identify successful transfectants in theabsence of glutamine in the media. In addition, theinclusion of methionine sulphoximine, an inhibitor ofglutamine synthetase activity, enables furtherselection of those clones producing relatively highlevels of transfected glutamine synthetase and henceany heterologous gene which is coupled to it. Theglutamine synthetase system technology has been usedfor research and development purposes during thisdecade and its importance is clearly demonstrated nowthat two therapeutic products produced using thissystem have reached the market place.

Keywords: gene amplification, glutamine synthetase, methioninesulphoximine, NS0, productivity, recombinant protein

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References

  1. Anon (1997) FDA advisory committee recommends Roche laboratories' Zenapax for the prevention of renal transplant rejection. Dialysis and Transplantation 26: 816.
  2. Apte SS, Olsen BR, Murphy G. The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J Biol Chem. 1995;270:14313–14318. doi: 10.1074/jbc.270.24.14313. [DOI] [PubMed] [Google Scholar]
  3. Ashford DA, Alafi CD, Gamble VM, Mackay DJG, Rademacher TW, Williams PJ, Dwek RA, Barclay AN, Davis SJ, Somoza C, Ward HA, Williams AF. Site-specific glycosylation of recombinant rat and human soluble CD4 variants expressed in Chinese hamster ovary cells. J Biol Chem. 1993;268:3260–3267. [PubMed] [Google Scholar]
  4. Baker K, Ison A, Freedman R, Jones W, James D. Realtime monitoring of recombinant protein concentration in animal cell cultures using an optical biosensor. Genetic Engineer Biotechnologist. 1997;17:69–74. [Google Scholar]
  5. Bebbington CR. Expression of antibody genes in nonlymphoid mammalian cells. Methods: A companion to Methods in Enzymology. 1991;2:136–145. [Google Scholar]
  6. Bebbington CR, Hentschel CCG. The use of vectors based on gene amplification for the expression of cloned genes in mammalian cells. In: Glover D, editor. DNA Cloning, Vol. III. New York: Academic Press; 1987. pp. 163–188. [Google Scholar]
  7. Bebbington CR, Renner G, Thomson S, King D, Abrams D, Yarranton GT. High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker. Bio/Technology. 1992;10:169–175. doi: 10.1038/nbt0292-169. [DOI] [PubMed] [Google Scholar]
  8. Berg EL, Fromm C, Melrose J, Tsurushita N. Antibodies cross-reactive with E-and P-selectin block both E-and P-selectin functions. Blood. 1995;85:31–37. [PubMed] [Google Scholar]
  9. Bibila T, Ranucci C, Glazomitsky K, Buckland B, Aunins J. Investigation of NS0 cell metabolic behavior in monoclonal antibody producing clones. Ann NY Acad Sci. 1994;745:277–284. doi: 10.1111/j.1749-6632.1994.tb44382.x. [DOI] [PubMed] [Google Scholar]
  10. Bibila TA, Ranucci CS, Glazomitsky K, Buckland BC, Aunins JG. Monoclonal antibody process development using medium concentrates. Biotechnol Prog. 1994;10:87–96. doi: 10.1021/bp00025a011. [DOI] [PubMed] [Google Scholar]
  11. Birch JR, Froud SJ. Mammalian cell culture systems for recombinant protein production. Biologicals. 1994;22:127–133. doi: 10.1006/biol.1994.1019. [DOI] [PubMed] [Google Scholar]
  12. Birch JR, Bebbington CR, Field R, Renner G, Brand H, Finney H. The production of recombinant antibodies using the glutamine synthetase (GS) system. In: Kaminogawa S, Ametani A, Hachimura S, editors. Animal Cell Technology: Basic and Applied Aspects, Vol. 5. Dordrecht: Kluwer Academic Publishers; 1993. pp. 573–577. [Google Scholar]
  13. Birch JR, Boraston RC, Metcalfe H, Brown ME, Bebbington CR, Field RP. Selecting and designing cell lines for improved physiological characteristics. Cytotechnology. 1994;15:11–16. doi: 10.1007/BF00762375. [DOI] [PubMed] [Google Scholar]
  14. Blochberger TC, Cooper C, Peretz D, Tatzelt J, Griffith OH, Baldwin MA, Prusiner SB. Prion protein expression in Chinese hamster ovary cells using a glutamine synthetase selection and amplification system. Protein Eng. 1997;10:1465–1473. doi: 10.1093/protein/10.12.1465. [DOI] [PubMed] [Google Scholar]
  15. Broad D, Boraston R, Rhodes M. Production of recombinant proteins in serum-free media. Cytotechnology. 1991;5:47–55. doi: 10.1007/BF00365533. [DOI] [PubMed] [Google Scholar]
  16. Brown MH, Barclay AN. Expression of immunoglobulin and scavenger receptor superfamily domains as chimeric proteins with domains 3 and 4 of CD4 for ligand analysis. Protein Eng. 1994;7:515–521. doi: 10.1093/protein/7.4.515. [DOI] [PubMed] [Google Scholar]
  17. Brown ME, Renner G, Field RP, Hassell T. Process development for the production of recombinant antibodies using the glutamine synthetase (GS) system. Cytotechnology. 1992;9:231–236. doi: 10.1007/BF02521750. [DOI] [PubMed] [Google Scholar]
  18. Burton DR, Pyati J, Koduri R, Sharp SJ, Thornton GB, Parren PWHI, Sawyer LSW, Hendry RM, Dunlop N, Nara PL, Lamacchia M, Garratty E, Stiehm ER, Bryson YJ, Cao Y, Moore JP, Ho DD, Barbas CF. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994;266:1024–1027. doi: 10.1126/science.7973652. [DOI] [PubMed] [Google Scholar]
  19. Butler M, Jenkins H. Nutritional aspects of the growth of animal cells in culture. J Biotechnol. 1989;12:97–110. [Google Scholar]
  20. Cannon-Carlson S, Varnerin J, Tsarbopoulos A, Jenh C-H, Cox MA, Chou C-C, Connelly N, Zavodny P, Tang JC-T. Expression, purification and characterization of recombinant human interleukin-13 from NS-0 cells. Protein Expression and Purification. 1998;12:239–248. doi: 10.1006/prep.1997.0835. [DOI] [PubMed] [Google Scholar]
  21. Castro MG, Tomasec P, Morrison E, Murray CA, Hodge P, Blanning P, Linton E, Lowry PJ, Lowenstein PR. Mitogenic effects and nuclear locatisation of procorticotrophin-releasing hormone expressed within stably transfected fibroblast cells (CHO-K1) Mol Cell Endocrinol. 1995;107:17–27. doi: 10.1016/0303-7207(94)03416-q. [DOI] [PubMed] [Google Scholar]
  22. Cazzola F, Saggin L, Callegaro L. Production of novel monoclonal antibodies against rabbit platelet factor-IV. Hybridoma. 1992;11:61–69. doi: 10.1089/hyb.1992.11.61. [DOI] [PubMed] [Google Scholar]
  23. Classon BJ, Brown MH, Garnett D, Somoza C, Barclay AN, Willis AC, Williams AF. The hinge region of the CD8α chain: structure, antigenicity, and utility in expression of immunoglobulin superfamily domains. Inter Immunol. 1992;4:215–225. doi: 10.1093/intimm/4.2.215. [DOI] [PubMed] [Google Scholar]
  24. Cloeckaert A, Zygmunt MS, Dubray G, Limet JN. Characterization of O-polysaccharide specific monoclonal antibodies derived from mice infected with the rough Brucella-Melitensis strain-B115. J Gen Microbiol. 1993;139:1551–1556. doi: 10.1099/00221287-139-7-1551. [DOI] [PubMed] [Google Scholar]
  25. Cloeckaert A, Zygmunt MS, Nicolle JC, Dubray G, Limet JN. O-chain expression in the rough Brucella-Melitensis strain-B115. Induction of 0–polysaccharide specific monoclonal antibodies and intracellular localization demonstrated by immunoelectron microscopy. J Gen Microbiol. 1992;138:1211–1219. doi: 10.1099/00221287-138-6-1211. [DOI] [PubMed] [Google Scholar]
  26. Cockett MI, Bebbington CR, Yarranton GT. High level expression of tissue inhibitor of metalloproteinases in Chinese hamster ovary cells using glutamine synthetase gene amplification. Bio/Technology. 1990;8:662–667. doi: 10.1038/nbt0790-662. [DOI] [PubMed] [Google Scholar]
  27. Cockett MI, Bebbington CR, Yarranton GT. The use of engineered E1A genes to transactiviate the hCMV-MIE promoter in permanent CHO cell lines. Nucleic Acids Res. 1991;19:319–325. doi: 10.1093/nar/19.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Cosgrove L, Lovrecz GO, Verkuylen A, Cavaleri L, Black LA, Bentley JD, Howlett GJ, Gray PP, Ward CW, McKern NM. Purification and properties of insulin receptor ectodomain from large-scale mammalian cell culture. Protein Expression and Purification. 1995;6:789–798. doi: 10.1006/prep.1995.0010. [DOI] [PubMed] [Google Scholar]
  29. Cowan NJ, Secher DS, Milstein C. Intracellular immunoglobulin chain synthesis in non-secreting variants of a mouse myeloma: detection of inactive light-chain messenger RNA. J Mol Biol. 1974;90:691–701. doi: 10.1016/0022-2836(74)90533-6. [DOI] [PubMed] [Google Scholar]
  30. Crook RB, Louie M, Deuel TF, Tomkins GM. Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells. J Biol Chem. 1978;253:6125–6131. [PubMed] [Google Scholar]
  31. Crouch E, Chang D, Rust K, Persson A, Heuser J. Recombinant pulmonary surfactant protein D. J Biol Chem. 1994;269:15808–15813. [PubMed] [Google Scholar]
  32. Davis SJ, Puklavec MJ, Ashford DA, Harlos K, Jones EY, Stuart DI, Williams AF. Expression of soluble recombinant glycoproteins with predefined glycosylation: application to the crystallization of the T-cell glycoprotein CD2. Protein Eng. 1993;6:229–232. doi: 10.1093/protein/6.2.229. [DOI] [PubMed] [Google Scholar]
  33. Davis SJ, Ward HA, Puklavec MJ, Willis AC, Williams AF, Barclay AN. High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. J Biol Chem. 1990;265:10410–10418. [PubMed] [Google Scholar]
  34. DiStefano DJ, Mark GE, Robinson DK. Feeding of nutrients delays apoptotic death in fed-batch cultures of recombinant NS0 myeloma cells. Biotechnol Lett. 1996;18:1067–1072. [Google Scholar]
  35. Dorai H, Moore GP. The effect of dihydrofolate reductase mediated gene amplification on the expression of transfected immunoglobulin genes. J Immunol. 1987;139:4232–4241. [PubMed] [Google Scholar]
  36. Downham MR, Farrell WE, Jenkins HA. Endoplasmic reticulum protein expression in recombinant NS0 myelomas grown in batch culture. Biotechnol Bioeng. 1996;51:691–696. doi: 10.1002/(SICI)1097-0290(19960920)51:6<691::AID-BIT7>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  37. Duncan PJ, Jenkins HA, Hobbs G. The effect of hyperosmotic conditions on growth and recombinant protein expression by NS0 myeloma cells in culture. Genetic Engineer Biotechnologist. 1997;17:75–78. [Google Scholar]
  38. Elliott WH. Adenosinetriphosphate in glutamine synthesis. Nature. 1948;161:128–129. [PubMed] [Google Scholar]
  39. Elliott WH. Studies on the enzymic synthesis of glutamine. Biochem J. 1951;49:106–112. doi: 10.1042/bj0490106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ellis JH, Barber KA, Tutt A, Hale C, Lewis AP, Glennie MJ, Stevenson GT, Crowe JS. Engineered anti-CD38 monoclonal antibodies for immunotherapy of multiple myeloma. J Immunol. 1995;155:925–937. [PubMed] [Google Scholar]
  41. Fahnestock ML, Johnson JL, Feldman RMR, Neveu JM, Lane WS, Bjorkman PJ. The MHC class 1 homolog encoded by human cytomegalovirus binds endogenous peptides. Immunity. 1995;3:583–590. doi: 10.1016/1074-7613(95)90129-9. [DOI] [PubMed] [Google Scholar]
  42. Fahnestock ML, Johnson JL, Feldman RMR, Tsomides TJ, Mayer J, Narhi LO, Bjorkman PJ. Effects of peptide length and composition on binding to an empty class 1 MHC heterodimer. Biochemistry. 1994;33:8149–8158. doi: 10.1021/bi00192a020. [DOI] [PubMed] [Google Scholar]
  43. Feany MB, Yee AG, Delvy ML, Buckley KM. The synaptic vesicle proteins SV2, synaptotagmin and synaptophysin are sorted to separate cellular compartments in CHO fibroblasts. J Cell Biol. 1993;123:575–584. doi: 10.1083/jcb.123.3.575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Feng B, Shiber SK, Max SR. Glutamine regulates glutamine synthetase expression in skeletal muscle cells in culture. J Cell Physiol. 1990;145:376–380. doi: 10.1002/jcp.1041450224. [DOI] [PubMed] [Google Scholar]
  45. Field RP, Brand H, Renner GL, Robertson HA & Boraston R (1991) Production of a chimeric antibody for tumour imaging and therapy from Chinese hamster ovary (CHO) and myeloma cells. In: Spier RE, Griffiths JB & Meignier B (eds.) Production of Biologicals from Animal Cells in Culture (pp. 742–744) Butterworth-Heinemann.
  46. Field R, Cockett M & Froud SJ (1989) Glutamine synthetase amplification of TIMP expression in CHO cells. In: Spier RE, Griffiths JB, Stephenne J & Crooy PJ (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses (pp. 195–197) Butterworth-Heinemann.
  47. Flesher AR, Marzowski J, Wang W-C, Raff HV. Fluorophore-labeled carbohydrate analysis of immunoglobulin fusion proteins: correlation of oligosaccharide content with in vivo clearance profile. Biotechnol Bioeng. 1995;46:399–407. doi: 10.1002/bit.260460502. [DOI] [PubMed] [Google Scholar]
  48. Froud SJ, Clements GJ, Doyle ME, Harris ELV, Lloyd C, Murray P, Preneta A, Stephens PE, Thompson S & Yarranton GT (1991) The development of a process for the production of HIV1 GP120 from recombinant cell lines. In: Spier RE, Griffiths JB & Meignier B (eds.) Production of Biologicals from Animal Cells in Culture (pp. 110–116) Butterworth-Heinemann.
  49. Galfrè G, Milstein C. Preparation of monoclonal antibodies: strategies and procedures. In: Langone JJ, Vunakis HV, editors. Methods in Enzymology, Vol. 73. New York: Academic Press; 1981. pp. 3–46. [DOI] [PubMed] [Google Scholar]
  50. Gastinel LN, Simister NE, Bjorkman PJ. Expression and crystallization of a soluble and functional form of an Fc receptor related to class I histocompatibility molecules. Proc Natl Acad Sci USA. 1992;89:638–642. doi: 10.1073/pnas.89.2.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ghebrehiwet B, Lu PD, Zhang WB, Lim BL, Eggleton P, Leigh LEA, Reid KBM, Peerschke EIB. Identification of functional domains on gC1Q-R, a cell surface protein that binds to the globular “heads” of C1Q, using monoclonal antibodies and synthetic peptides. Hybridoma. 1996;15:333–342. doi: 10.1089/hyb.1996.15.333. [DOI] [PubMed] [Google Scholar]
  52. Gjörloff A, Hedlund G, Kalland T, Sansom D, Fischer H, Trowsdale J, Sjögren HO, Dohlsten M. The LFA-3 adhesion pathway is differently utilized by superantigen-activated human CD4+ T-cell subsets. Scand J Immunol. 1992;36:243–250. doi: 10.1111/j.1365-3083.1992.tb03096.x. [DOI] [PubMed] [Google Scholar]
  53. Gloor S, Nasse K, Essen LO, Appel F. Production and secretion in CHO cells of the extracellular domain of AMOG/β2, a type-II membrane protein. Gene. 1992;120:307–312. doi: 10.1016/0378-1119(92)90111-2. [DOI] [PubMed] [Google Scholar]
  54. Gofton CM, Roberts G, Bergin S & Owens RJ (1992) The rapid production of recombinant rabbit metalloproteinases in myeloma cells. In: Spier RE, Griffiths, JB & MacDonald C (eds.) Animal Cell Technology: Developments, Processes and Products (pp. 48–50) Butterworth-Heinemann.
  55. Gould S, DiStefano D, Cuca G, Robinson D, Silberklang M. Major metabloic changes accompany transfection and selection for high level expression of recombinant genes. In Vitro Cell Dev Biol. 1992;28:162A. [Google Scholar]
  56. Green NS, Rabinowitz JL, Zhu MH, Kobrin BJ, Scharff MD. Immunoglobulin variable region hypermutation in hybrids derived from a pre-B-cell line and a myeloma cell line. Proc Natl Acad Sci USA. 1995;92:6304–6308. doi: 10.1073/pnas.92.14.6304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Guerini D, Schröder S, Foletti D, Carafoli E. Isolation and characterization of a stable Chinese hamster ovary cell line overexpression the plasma membrane Ca2+-ATPase. J Biol Chem. 1995;270:14643–14650. doi: 10.1074/jbc.270.24.14643. [DOI] [PubMed] [Google Scholar]
  58. Gutman O, Danieli T, White JM, Henis YI. Effects of exposure to low pH on the lateral mobility of influenza hemagglutinin expressed at the cell surface: correlation between mobility inhibition and inactiviation. Biochemistry. 1993;32:101–106. doi: 10.1021/bi00052a014. [DOI] [PubMed] [Google Scholar]
  59. Hamilton AA, Manuel DM, Grundy JE, Turner AJ, King SI, Adair JR, White P, Carr FJ, Harris WJ. A humanized antibody against human cytomegalovirus (CMV) gpUL75 (gH) for prophylaxis or treatment of CMV infections. J Infect Dis. 1997;176:59–68. doi: 10.1086/514040. [DOI] [PubMed] [Google Scholar]
  60. Harfst E, Johnstone AP. Characterization of the glutamine synthetase amplifiable eukaryotic expression system applied to an integral membrane protein-the human thyrotrophin receptor. Anal Biochem. 1992;207:80–84. doi: 10.1016/0003-2697(92)90504-z. [DOI] [PubMed] [Google Scholar]
  61. Harfst E, Johnstone AP, Gout I, Taylor AH, Waterfield MD, Nussey SS. The use of the amplifiable high-expression vector pEE14 to study the interactions of autoantibodies with recombinant human thyrotropin receptor. Mol Cell Endocrinol. 1992;83:117–123. doi: 10.1016/0303-7207(92)90152-v. [DOI] [PubMed] [Google Scholar]
  62. Harfst E, Johnstone AP, Nussey SS. Characterization of the extracellular region of the human thyrotrophin receptor expressed as a recombinant protein. J Mol Endocrinol. 1992;9:227–236. doi: 10.1677/jme.0.0090227. [DOI] [PubMed] [Google Scholar]
  63. Harfst E, Johnstone AP, Nussey SS. Interaction of thyrotropin and thyroid-stimulating antibodies with recombinant extracellular region of the human TSH receptor. Lancet. 1992;339:193–194. doi: 10.1016/0140-6736(92)90273-6. [DOI] [PubMed] [Google Scholar]
  64. Hassell T, Brand H, Renner G, Westlake A & Field RP (1992) Stability of production of recombinant antibodies from glutamine synthetase amplified CHO and NS0 cell lines. In: Spier RE, Griffiths, JB & MacDonald C (eds.) Animal Cell Technology: Developments, Processes & Products (pp. 42–47) Butterworth-Heinemann.
  65. Haumont M, Jacquet A, Massaer M, Deleersnyder V, Mazzu P, Bollen A, Jacobs P. Purification, characterization and immunogenicity of recombinant varicella-zoster virus glycoprotein gE secreted by Chinese hamster ovary cells. Virus Res. 1996;40:199–204. doi: 10.1016/0168-1702(95)01270-2. [DOI] [PubMed] [Google Scholar]
  66. Hendershot L, Bole D, Köhler G, Kearney JF. Assembly and secretion of heavy chains that do not associate posttranslationally with immunoglobulin heavy chain-binding protein. J Cell Biol. 1987;104:761–767. doi: 10.1083/jcb.104.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Hirayama F, Katayama N, Neben S, Donaldson D, Nickbarg EB, Clark SC, Ogawa M. Synergistic interaction between interleukin-12 and steel factor in support of proliferation of murine lymphohematopoietic progenitors in culture. Blood. 1994;83:92–98. [PubMed] [Google Scholar]
  68. Hodgson J. Expression systems: a user's guide. Bio/Technology. 1993;11:887–893. doi: 10.1038/nbt0893-887. [DOI] [PubMed] [Google Scholar]
  69. Horibata K, Harris AW. Mouse myelomas and lymphomas in culture. Exp Cell Res. 1970;60:61–77. doi: 10.1016/0014-4827(70)90489-1. [DOI] [PubMed] [Google Scholar]
  70. Hovey A, Bebbington CR, Jenkins N. Control of growth and recombinant protein synthesis by heat-shock in a mutant mammalian cell line. Biotechnol Lett. 1994;16:215–220. [Google Scholar]
  71. Hovey A, Bebbington C & Jenkins N (1994b) Simultaneous control of growth and productivity using a mutant CHO cell line. In: Spier RE, Griffiths JB & Berthold W(eds.) Animal Cell Technology: Products of Today, Prospects for Tomorrow (pp. 422–424) Butterworth-Heinemann.
  72. Jenkins N, Hovey A. Generation of CHO cell mutants for growth control. In: Kaminogawa S, Ametani A, Hachimura S, editors. Animal Cell Technology: Basic and Applied Aspects, Vol 5. Dordrecht: Kluwer Academic Publishers; 1993. pp. 267–272. [Google Scholar]
  73. Jenkins N, Hovey A. Temperature control of growth and productivity in mutant Chinese hamster ovary cells synthesizing a recombinant protein. Biotechnol Bioeng. 1993;42:1029–1036. doi: 10.1002/bit.260420903. [DOI] [PubMed] [Google Scholar]
  74. Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang S-C, Dormitzer M, O'Grady J, Koenig S, Tamura JK, Woods R, Bansal G, Couchenour D, Tsao E, Hall WC, Young JF. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis. 1997;176:1215–1224. doi: 10.1086/514115. [DOI] [PubMed] [Google Scholar]
  75. Kadesch T, Berg P. Effects of the position of the simian virus 40 enhancer on expression of multiple transcription units in a single plasmid. Mol Cell Biol. 1986;6:2593–2601. doi: 10.1128/mcb.6.7.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Kaufman RJ, Wasley LC, Spiliotes AJ, Gossels SD, Latt SA, Larsen GR, Kay RM. Coamplification and coexpression of human tissue-type plasminogen activator and murine dihydrofolate reductase sequences in Chinese hamster ovary cells. Mol Cell Biol. 1985;5:1750–1759. doi: 10.1128/mcb.5.7.1750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Keen MJ, Hale C. The use of serum-free medium for the production of functionally active humanised monoclonal antibody from NS0 mouse myeloma cells engineered using glutamine synthetase as a selectable marker. Cytotechnology. 1996;18:207–217. doi: 10.1007/BF00767768. [DOI] [PubMed] [Google Scholar]
  78. Keen MJ, Steward TW. Adaptation of cholesterol-requiring NS0 mouse myeloma cells to high density growth in a fully defined protein-free and cholesterol-free culture medium. Cytotechnology. 1995;17:203–211. doi: 10.1007/BF00749658. [DOI] [PubMed] [Google Scholar]
  79. Kemble GW, Henis YI, White JM. GPI-and transmembrane-anchored influenza hemagglutinin differ in structure and receptor binding activity. J Cell Biol. 1993;122:1253–1265. doi: 10.1083/jcb.122.6.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Kim CH, Oh Y, Lee TH. Codon optimization for high-level expression of human erythropoietin (EPO) in mammalian cells. Gene. 1997;199:293–301. doi: 10.1016/s0378-1119(97)00384-3. [DOI] [PubMed] [Google Scholar]
  81. King DJ, Antoniw P, Owens RJ, Adair JR, Haines AMR, Farnsworth APH, Finney H, Lawson ADG, Lyons A, Baker TS, Baldock D, Mackintosh J, Gofton C, Yarranton GT, McWilliams W, Shochat D, Leichner PK, Welt S, Old LJ, Mountain A. Preparation and preclinical evaluation of humanised A33 immunoconjugates for radioimmunotherapy. British J Cancer. 1995;72:1364–1372. doi: 10.1038/bjc.1995.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. King DJ, Byron OD, Mountain A, Weir N, Harvey A, Lawson ADG, Proudfoot KA, Baldock D, Harding SE, Yarranton GT, Owens RJ. Expression, purification and characterization of B72.3 Fv fragments. Biochem J. 1993;290:723–729. doi: 10.1042/bj2900723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Kingston RE, Kaufman RJ, Bebbington CR & Rolfe MR (1994) Amplification using CHO cell expression vectors. In: Ausubel FM et al. (eds.) Current Protocols in Molecular Biology. Unit 16.14 (pp. 16.14.1–16.14.13). [DOI] [PubMed]
  84. Knäuper V, López-Otin C, Smith B, Knight G, Murphy G. Biochemical characterization of human collagenase-3. J Biol Chem. 1996;271:1544–1550. doi: 10.1074/jbc.271.3.1544. [DOI] [PubMed] [Google Scholar]
  85. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  86. Köhler G, Milstein C. Derivation of specific antibodyproducing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976;6:511–519. doi: 10.1002/eji.1830060713. [DOI] [PubMed] [Google Scholar]
  87. Köhler G, Howe SC, Milstein C. Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. Eur J Immunol. 1976;6:292–295. doi: 10.1002/eji.1830060411. [DOI] [PubMed] [Google Scholar]
  88. Konstantinov KB. Monitoring and control of the physiological state of cell cultures. Biotechnol Bioeng. 1996;52:271–289. doi: 10.1002/bit.260520203. [DOI] [PubMed] [Google Scholar]
  89. Kucherlapati R, Skoultchi AI. Introduction of purified genes into mammalian cells. CRC Crit Rev Biochem. 1984;16:349–379. doi: 10.3109/10409238409108719. [DOI] [PubMed] [Google Scholar]
  90. Lange G, Lewis SJ, Murshudov GN, Dodson GG, Moody PCE, Turkenburg JP, Barclay AN, Brady RL. Crystal structure of an extracellular fragment of the rat CD4 receptor containing domains 3 and 4. Structure. 1994;2:469–481. doi: 10.1016/s0969-2126(00)00048-4. [DOI] [PubMed] [Google Scholar]
  91. Laubach VE, Garvey EP, Sherman PA. High-level expression of human inducible nitric oxide synthase in Chinese hamster ovary cells and characterization of the purified enzyme. Biochem Biophys Res Commun. 1996;218:802–807. doi: 10.1006/bbrc.1996.0143. [DOI] [PubMed] [Google Scholar]
  92. Levintow L, Meister A. Reversibility of the enzymatic synthesis of glutamine. J Biol Chem. 1954;209:265–280. [PubMed] [Google Scholar]
  93. Lifely MR, Hale C, Boyce S, Keen MJ, Phillips J. Glycosylation and biological activity of CAMPATH-1H expressed in different cell lines and grown under different culture conditions. Glycobiology. 1995;5:813–822. doi: 10.1093/glycob/5.8.813. [DOI] [PubMed] [Google Scholar]
  94. Lonza Press Release (1998) http://www.lonza.com/framer5.2.html
  95. Lyaku JRS, Sinclair JA, Nettleton PF, Marsden HS. Production and characterization of monoclonal antibodies to cervine herpesvirus-1. Vet Microbiol. 1992;32:229–239. [PubMed] [Google Scholar]
  96. Manning JM, Moore S, Rowe WB, Meister A. Identification of L-methionine S-sulfoximine as the disterioisomer of L-methionine SR-sulfoximine that inhibits glutamine synthetase. Biochemistry. 1969;8:2681–2685. doi: 10.1021/bi00834a066. [DOI] [PubMed] [Google Scholar]
  97. McAlister MSB, Brown MH, Willis AC, Rudd PM, Harvey DJ, Aplin R, Shotton DM, Dwek RA, Barclay AN, Driscoll PC. Structural analysis of the CD5 antigen. Eur J Biochem. 1998;257:131–141. doi: 10.1046/j.1432-1327.1998.2570131.x. [DOI] [PubMed] [Google Scholar]
  98. McAlister MSB, Davis B, Pfuhl M, Driscoll PC. NMR analysis of the N-terminal SRCR domain of human CD5: engineering of a glycoprotein for superior characteristics in NMR experiments. Protein Eng. 1998;11:847–853. doi: 10.1093/protein/11.10.847. [DOI] [PubMed] [Google Scholar]
  99. McCall MN, Shotton DM, Barclay AN. Expression of soluble isoforms of rat CD45. Analysis by electron microscopy and use in epitope mapping of anti-CD45R monoclonal antibodies. Immunology. 1992;76:310–317. [PMC free article] [PubMed] [Google Scholar]
  100. McInnes C, Haig D, Logan M. The cloning and expression of the gene for ovine interleukin-3 (multi-CSF) and a comparison of the in vitro hematopoietic activity of ovine IL-3 with ovine GM-CSF and human M-CSF. Exp Hematol. 1993;21:1528–1534. [PubMed] [Google Scholar]
  101. McKnight AJ, Classon BJ. Biochemical and immunological properties of rat recombinant interleukin-2 and interleukin-4. Immunology. 1992;75:286–292. [PMC free article] [PubMed] [Google Scholar]
  102. Meister A. Glutamine synthetase of mammals. The Enzymes. 1974;X:699–754. [Google Scholar]
  103. Meister A (1980) Catalytic mechanism of glutamine synthetase; overview of glutamine metabolism. In: Mora J & Palacios R (eds.) Glutamine: Metabolism, Enzymology and Regulation (pp. 1–40) Academic Press.
  104. Mercille S, Massie B. Induction of apoptosis in nutrientdeprived cultures of hybridoma and myeloma cells. Biotechnol Bioeng. 1994;44:1140–1154. doi: 10.1002/bit.260440916. [DOI] [PubMed] [Google Scholar]
  105. Midelfort CF, Rose IA. A stereochemical method for detection of ATP terminal phosphate transfer in enzymatic reactions. J Biol Chem. 1976;251:5881–5887. [PubMed] [Google Scholar]
  106. Miller RE, Hackenberg R, Gershman H. Regulation of glutamine synthetase in cultured 3T3–L1 cells by insulin, hydrocortisone, and dibutyryl cyclic AMP. Proc Natl Acad Sci USA. 1978;75:1418–1422. doi: 10.1073/pnas.75.3.1418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Moore JP, McKeating JA, Jones IM, Stephens PE, Clements G, Thomson S, Weiss RA. Characterization of recombinant gp 120 and gp 160 from HIV-1: binding to monoclonal antibodies and soluble CD4. AIDS. 1989;4:307–315. doi: 10.1097/00002030-199004000-00004. [DOI] [PubMed] [Google Scholar]
  108. Morrison E, Tomasec P, Linton EA, Lowry PJ, Lowenstein PR, Castro MG. Expression of biologically active procorticotrophin-releasing hormone (proCRH) in stably transfected CHO-K1 cells: characterization of nuclear proCRH. J Neuroendocrinol. 1995;7:263–272. doi: 10.1111/j.1365-2826.1995.tb00756.x. [DOI] [PubMed] [Google Scholar]
  109. Murphy G, Allan JA, Willenbrock F, Cockett MI, O'Connell JP, Docherty AJP. The role of the C-terminal domain in collagenase and stromelysin specificty. J Biol Chem. 1992;267:9612–9618. [PubMed] [Google Scholar]
  110. Murphy G, Cockett MI, Ward RV, Docherty AJP. Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. Biochem J. 1991;277:277–279. doi: 10.1042/bj2770277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  111. Murphy G, Houbrechts A, Cockett MI, Williamson RA, O'Shea M, Docherty AJP. The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity. Biochemistry. 1991;30:8097–8102. doi: 10.1021/bi00247a001. [DOI] [PubMed] [Google Scholar]
  112. Murphy G, Willenbrock F, Ward RV, Cockett MI, Eaton D, Docherty AJP. The C-terminal domain of 72kDa gelatinase A is not required for catalysis, but is essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases. Biochem J. 1992;283:637–641. doi: 10.1042/bj2830637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Murray K, Ang C-E, Gull K, Hickman JA, Dickson AJ. NS0 myeloma cell death: influence of bcl-2 overexpression. Biotechnol Bioeng. 1996;51:298–304. doi: 10.1002/(SICI)1097-0290(19960805)51:3<298::AID-BIT5>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  114. Nakaki T, Deans RJ, Lee AS. Enhanced transcription of the 78,000–dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1) Mol Cell Biol. 1989;9:2233–2238. doi: 10.1128/mcb.9.5.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Nguyen Q, Murphy G, Hughes CE, Mort JS, Roughley PJ. Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Biochem J. 1993;295:595–598. doi: 10.1042/bj2950595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Orlinick JR, Elkon KB, Chao MV. Separate domains of the human Fas ligand dictate self-association and receptor binding. J Biol Chem. 1997;272:32221–32229. doi: 10.1074/jbc.272.51.32221. [DOI] [PubMed] [Google Scholar]
  117. Ortlepp S, Stephens PE, Hogg N, Figdor CG, Robinson MK. Antibodies that activate β2 integrins can generate different ligand binding states. Eur J Immunol. 1995;25:637–643. doi: 10.1002/eji.1830250302. [DOI] [PubMed] [Google Scholar]
  118. O'Shea M, Willenbrock F, Williamson RA, Cockett MI, Freedman RB, Reynolds JJ, Docherty AJP, Murphy G. Sitedirected mutations that alter the inhibitory activity of the tissue inhibitor of metalloproteinases-1: importance of the N-terminal region between cysteine 3 and cysteine 13. Biochemistry. 1992;31:10146–10152. doi: 10.1021/bi00157a002. [DOI] [PubMed] [Google Scholar]
  119. Owens RJ, King DJ, Howat D, Lisle H, Mountain A, Harvey A, Bergin S, Turner A, Pedley B, Boden J, Begent R, Yarranton GT. Tumor binding properties of B72.3 Fv fragments. Antibody, Immunoconjugates and Radiopharmaceuticals. 1991;4:459–467. [Google Scholar]
  120. Page MJ (1988) Expression of foreign genes in mammalian cells. In: Walker JM (ed.) Methods in Molecular Biology, Vol 4, New Nucleic Acid Techniques (pp. 371–384) The Humana Press. [DOI] [PubMed]
  121. Page MJ, Sydenham MA. High level expression of the humanized monoclonal antibody CAMPATH-1H in Chinese hamster ovary cells. Bio/Technology. 1991;9:64–68. doi: 10.1038/nbt0191-64. [DOI] [PubMed] [Google Scholar]
  122. Pallavicini MG, DeTeresa PS, Rosette C, Gray JW, Wurm FM. Effects of methotrexate on transfected DNA stability in mammalian cells. Mol Cell Biol. 1990;10:401–404. doi: 10.1128/mcb.10.1.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Paterson T, Innes J, McMillan L, Downing I, McCann Carter MC. Variation in IgG1 heavy chain allotype does not contribute to differences in biological activity of two human anti-rhesus (D) monoclonal antibodies. Immunotech. 1998;4:37–47. doi: 10.1016/s1380-2933(98)00005-0. [DOI] [PubMed] [Google Scholar]
  124. Peakman TC, Worden J, Harris RH, Cooper H, Tite J, Page MJ, Gewert DR, Bartholemew M, Crowe JS, Brett S. Comparison of expression of a humanized monoclonal antibody in mouse NS0 myeloma cells and Chinese hamster ovary cells. Hum Antibod Hybridomas. 1994;5:65–74. [PubMed] [Google Scholar]
  125. Pearce A, Downham MR, Farrell WE, Jenkins HA. Characterisation of the isoforms of GRP78 in a recombinant myeloma cell line. Genetic Engineer Biotechnologist. 1995;15:285–287. [Google Scholar]
  126. Pilson RS, Levin W, Desai B, Reik LM, Lin P, Korkmaz-Duffy E, Campbell E, Tso JY, Kerwin JA, Hakimi J. Bispecific humanized anti-IL-2 receptor αβ antibodies inhibitory for both IL-2–and IL-15–mediated proliferation. J Immunol. 1997;159:1543–1556. [PubMed] [Google Scholar]
  127. Porro G, Bonardi MA, Giovanetti E, Lento P, Modena D. Production and characterization of monoclonal antibodies against the ribosome inactivating proteins dianthin32 and momochin. Hybridoma. 1994;13:99–105. doi: 10.1089/hyb.1994.13.99. [DOI] [PubMed] [Google Scholar]
  128. Potter M, Boyce CR. Induction of plasma cell neoplasma in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature. 1962;193:1086–1087. doi: 10.1038/1931086a0. [DOI] [PubMed] [Google Scholar]
  129. Potter M, MacCardle RC. Histology of developing plasma cell neoplasia induced by mineral oil in BALB/c mice. J Natl Cancer Instit. 1964;33:497–515. [PubMed] [Google Scholar]
  130. Potter M, Appella E, Geisser S. Variations in the heavy polypeptide chain structure of gamma myeloma immunoglobulins from an inbred strain of mice and a hypothesis as to their origin. J Mol Biol. 1965;14:361–372. doi: 10.1016/s0022-2836(65)80187-5. [DOI] [PubMed] [Google Scholar]
  131. Proudfoot NJ. Transcriptional interference and termination between duplicated α-globin gene constructs suggests a novel mechanism for gene regulation. Nature. 1986;322:562–565. doi: 10.1038/322562a0. [DOI] [PubMed] [Google Scholar]
  132. Pu H, Young AP. The structure of the chicken glutamine synthetase-encoding gene. Gene. 1989;81:169–175. doi: 10.1016/0378-1119(89)90348-x. [DOI] [PubMed] [Google Scholar]
  133. Pu H, Cashion LM, Kretschmer PJ, Liu Z. Rapid establishment of high-producing cell lines using dicistronic vectors with glutamine synthetase as the selection marker. Mol Biotechnol. 1998;10:17–25. doi: 10.1007/BF02745860. [DOI] [PubMed] [Google Scholar]
  134. Quilliam AL, Osman N, McKenzie IFC, Hogarth PM. Biochemical characterization of murine Fc RI. Immunology. 1993;78:358–363. [PMC free article] [PubMed] [Google Scholar]
  135. Ramasamy R, Munro A, Milstein C. Possible role for the Fc receptor on B lymphocytes. Nature. 1974;249:573–574. doi: 10.1038/249573a0. [DOI] [PubMed] [Google Scholar]
  136. Ray NG, Rivera R, Gupta R, Mueller D. Large-scale production of humanized monoclonal antibody expressed in a GS-NS0 cell line. In: Carrondo MJT, Griffiths B, Moreira JLP, editors. Animal Cell Technology. Dordrecht: Kluwer Academic Publishers; 1997. pp. 235–241. [Google Scholar]
  137. Reimann KA, Lin W, Bixler S, Browning B, Ehrenfels BN, Lucci J, Miatkowski K, Olson D, Parish TH, Rosa MD, Oleson FB, Hsu YM, Padlan EA, Letvin NL, Burkly LC. A humanized form of a CD4–specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties. AIDS Research and Human Retroviruses. 1997;13:933–943. doi: 10.1089/aid.1997.13.933. [DOI] [PubMed] [Google Scholar]
  138. Reitzer LJ, Wice BM, Kennell D. Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem. 1979;254:2669–2676. [PubMed] [Google Scholar]
  139. Rhode PR, Burkhardt M, Jiao J, Siddiqui AH, Huang GP, Wong HC. Single-chain MHC class II molecules induce T cell activation and apoptosis. J Immunol. 1996;157:4885–4891. [PubMed] [Google Scholar]
  140. Richards CM, Aucken HA, Tucker EM, Hannant D, Mumford JA, Powell JR. The production of equine monoclonal immunoglobulins by horse mouse heterohybridomas. Vet Immunol Immunopathol. 1992;33:129–143. doi: 10.1016/0165-2427(92)90040-w. [DOI] [PubMed] [Google Scholar]
  141. Robinson MK, Andrew D, Rosen H, Brown D, Ortlepp S, Stephens P, Butcher EC. Antibody against the Leu-CAM β-chain (CD18) promotes both LFA-1–and CR3–dependent adhesion events. J Immunol. 1992;148:1080–1085. [PubMed] [Google Scholar]
  142. Robinson DK, Chan CP, Yu Ip CC, Seamans TC, Lee DK, Lenny AB, Tung J-S, DiStefano DJ, Munshi S, Gould SL, Tsai PK, Irwin J, Mark GE & Silberklang M (1994b) Product consistency during long-term fed-batch culture. In: Spier RE, Griffiths JB & Berthold W (eds.) Animal Cell Technology: Products of Today, Prospects for Tomorrow (pp. 763–767) Butterworth-Heinemann.
  143. Robinson DK, Chan CP, Yu Ip C, Tsai PK, Tung J, Seamans TC, Lenny AB, Lee DK, Irwin J, Silberklang M. Characterization of a recombinant antibody produced in the course of a high yield fed-batch process. Biotechnol Bioeng. 1994;44:727–735. doi: 10.1002/bit.260440609. [DOI] [PubMed] [Google Scholar]
  144. Robinson DK, DiStefano D, Gould SL, Cuca G, Seamans TC, Benincasa D, Munshi S, Chan CP, Stafford-Hollis J, Hollis GF, Jain D, Ramasubramanyan K, Mark GE & Siberklang M (1995) Production of engineered antibodies in myeloma and hybridoma cells. Enhancements in gene expression and process design. In: Wang H & Imanaka (eds.) Antibody Engineering. American Chemical Society Symposium Series 604 (pp. 1–14) Washington DC.
  145. Robinson DK, Seamans TC, Gould SL, DiStefano DJ, Chan CP, Lee DK, Bibila T, Glazomitsky K, Munshi S, Daugherty B, O'Neill L, Palladino J, Stafford-Hollis J, Hollis GF, Silberklang M. Optimization of a fed-batch process for production of a recombinant antibody. Ann NY Acad Sci. 1994;745:285–296. doi: 10.1111/j.1749-6632.1994.tb44383.x. [DOI] [PubMed] [Google Scholar]
  146. Ronzio RA, Meister A. Phosphorylation of methionine sulfoximine by glutamine synthetase. Biochemistry. 1968;59:164–170. doi: 10.1073/pnas.59.1.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  147. Ronzio RA, Rowe WB, Meister A. Studies on the mechanism of inhibition of glutamine synthetase by methionine sulfoximine. Biochemistry. 1969;8:1066–1075. doi: 10.1021/bi00831a038. [DOI] [PubMed] [Google Scholar]
  148. Rossmann C, Sharp N, Allen G, Gewert D. Expression and purification of recombinant, glycosylated human interferon alpha 2b in murine myeloma NS0 cells. Protein Expression and Purification. 1996;7:335–342. doi: 10.1006/prep.1996.0050. [DOI] [PubMed] [Google Scholar]
  149. Rowe WB, Meister A. Studies on the inhibition of glutamine synthetase by methionine sulfone. Biochemistry. 1973;12:1578–1582. doi: 10.1021/bi00732a018. [DOI] [PubMed] [Google Scholar]
  150. Rowe WB, Ronzio RA, Meister A. Inhibition of glutamine synthetase by methionine sulfoximine. Studies on methionine sulfoximine phosphate. Biochemistry. 1969;8:2674–2680. doi: 10.1021/bi00834a065. [DOI] [PubMed] [Google Scholar]
  151. Salas MA, Brown OA, Perone MJ, Castro MG, Goya RG. Effect of the corticotrophin releasing hormone precursor on interleukin-6 release by human mononuclear cells. Clinical Immunol and Immunopathol. 1997;85:35–39. doi: 10.1006/clin.1997.4395. [DOI] [PubMed] [Google Scholar]
  152. Shi J, Ghirlando R, Beavil RL, Beavil AJ, Keown MB, Young RJ, Owens RJ, Sutton BJ, Gould HJ. Interaction of the low-affinity receptor CD23/Fc∈RII lectin domain with the Fc∈3–4 fragment of human immunoglobulin E. Biochemistry. 1997;36:2112–2122. doi: 10.1021/bi961231e. [DOI] [PubMed] [Google Scholar]
  153. Siemers NO, Kerr DE, Yarnold S, Stebbins MR, Vrudhula VM, Hellström I, Hellström KE, Senter PD. Construction, expression, and activities of L49–sFv-β-lactamase, a single-chain antibody fusion protein for anticancer prodrug activiation. Bioconjugate Chem. 1997;8:510–519. doi: 10.1021/bc9700751. [DOI] [PubMed] [Google Scholar]
  154. Simonsen CC, McGrogan M. The molecular biology of production cell lines. Biologicals. 1994;22:85–94. doi: 10.1006/biol.1994.1014. [DOI] [PubMed] [Google Scholar]
  155. Sims MJ, Hassal DG, Brett S, Rowan W, Lockyer MJ, Angel A, Lewis AP, Hale G, Waldmann H, Crowe JS. A humanized CD18 antibody can block function without cell destruction. J Immunol. 1993;151:2296–2308. [PubMed] [Google Scholar]
  156. Skonier J, Bennett K, Rothwell V, Kosowski S, Plowman G, Wallace P, Edelhoff S, Disteche C, Neubauer M, Marquardt H, Rodgers J, Purchio AF. βig-h3: A transforming growth factor-β-responsive gene encoding a secreted protein that inhibits cell attachment in vitro and suppresses the growth of CHO cells in nude mice. DNA Cell Biol. 1994;13:571–583. doi: 10.1089/dna.1994.13.571. [DOI] [PubMed] [Google Scholar]
  157. Speck JF. The enzymic synthesis of glutamine. J Biol Chem. 1947;168:403–404. [PubMed] [Google Scholar]
  158. Speck JF. The enzymatic synthesis of glutamine, a reaction utilizing adenosine triphosphate. J Biol Chem. 1949;179:1405–1426. [PubMed] [Google Scholar]
  159. Stanley P, Hogg N. The I domain of integrin LFA-1 interacts with ICAM-1 domain 1 at residue Glu-34 but not Gln-73. J Biol Chem. 1998;273:3358–3362. doi: 10.1074/jbc.273.6.3358. [DOI] [PubMed] [Google Scholar]
  160. Stark GR, Wahl GM. Gene amplification. Ann Rev Biochem. 1984;53:447–491. doi: 10.1146/annurev.bi.53.070184.002311. [DOI] [PubMed] [Google Scholar]
  161. Stephens S, Emtage S, Vetterlein O, Chaplin L, Bebbington C, Nesbitt A, Sopwith M, Athwal D, Novak C, Bodmer M. Comprehensive pharmacokinetics of a humanized antibody and analysis of residual anti-idiotypic responses. Immunology. 1995;85:668–674. [PMC free article] [PubMed] [Google Scholar]
  162. Tan JC, Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, Narula SK, Zavodny PJ, Chou C-C. Characterization of recombinant extracellular domain of human interleukin-10 receptor. J Biol Chem. 1995;270:12906–12911. doi: 10.1074/jbc.270.21.12906. [DOI] [PubMed] [Google Scholar]
  163. Thole HH, Jakob F. Characterization of 5 monoclonal antibodies raised against domain-E of the porcine estradiol-receptor. Experimental Clin Endocrinol. 1993;101:112–118. doi: 10.1055/s-0029-1211216. [DOI] [PubMed] [Google Scholar]
  164. Todhunter JA, Purich DL. Use of the sodium borohydride reduction technique to identify a γ-glutamyl phosphate intermediary in the Escherichia coli glutamine synthetase reaction. J Biol Chem. 1975;250:3505–3509. [PubMed] [Google Scholar]
  165. Trowbridge IS, Johnson P, Ostergaard H, Hole N. Structure and function of CD45: a leukocyte-specific protein tyrosine phosphatase. Adv Exp Med Biol. 1992;323:29–37. doi: 10.1007/978-1-4615-3396-2_5. [DOI] [PubMed] [Google Scholar]
  166. Urlaub G, Chasin LA. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci USA. 1980;77:4216–4220. doi: 10.1073/pnas.77.7.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  167. Van der Merwe PA, McPherson DC, Brown MH, Barclay AN, Cyster JG, Williams AF, Davis SJ. The NH2-terminal domain of rat CD2 binds rat CD48 with a low affinity and binding does not require glycosylation of CD2. Eur J Immunol. 1993;23:1373–1377. doi: 10.1002/eji.1830230628. [DOI] [PubMed] [Google Scholar]
  168. Weidle UH, Buckel P, Wienberg J. Amplified expression constructs for human tissue-type plasminogen activator in Chinese hamster ovary cells: instability in the absence of selective pressure. Gene. 1988;66:193–203. doi: 10.1016/0378-1119(88)90356-3. [DOI] [PubMed] [Google Scholar]
  169. Willenbrock F, Crabbe T, Slocombe PM, Sutton CW, Docherty AJP, Cockett MI, O'Shea M, Brocklehurst K, Phillips IR, Murphy G. The activity of the tissue inhibitors of metalloproteinases is regulated by C-terminal domain interactions: a kinetic analysis of the inhibition of gelatinase A. Biochemistry. 1993;32:4330–4337. doi: 10.1021/bi00067a023. [DOI] [PubMed] [Google Scholar]
  170. Williams AF, Davis SJ, He Q, Barclay AN. Structural diversity in domains of the immunoglobulin superfamily. Cold Springs Harb, Quart Biol. 1989;54:637–647. doi: 10.1101/sqb.1989.054.01.075. [DOI] [PubMed] [Google Scholar]
  171. Yoon S-J, Konstantinov KB. Continuous, real-time monitoring of the oxygen uptake rate (OUR) in animal cell bioreactors. Biotechnol Bioeng. 1994;44:983–990. doi: 10.1002/bit.260440815. [DOI] [PubMed] [Google Scholar]
  172. Young RJ, Owens RJ, MacKay GA, Chan CMW, Shi J, Hide M, Francis DM, Henry AJ, Sutton BJ, Gould HJ. Secretion of recombinant human IgE-Fc by mammalian cells and biological activity of glycosylation site mutants. Protein Eng. 1995;8:193–199. doi: 10.1093/protein/8.2.193. [DOI] [PubMed] [Google Scholar]
  173. Yu Ip CC, Miller WJ, Silberklang M, Mark GE, Ellis RW, Huang L, Glushka J, van Halbeek H, Zhu J, Alhadeff JA. Structural characterization of the N-glycans of a humanized anti-CD18 murine immunoglobulin G. Arch Biochem Biophys. 1994;308:387–399. doi: 10.1006/abbi.1994.1055. [DOI] [PubMed] [Google Scholar]
  174. Zhou W, Bibila T, Glazomitsky K, Montalvo J, Chan C, DiStefano D, Munshi S, Robinson D, Buckland B, Aunins J. Large scale production of recombinant mouse and rat growth hormone by fed-batch GS-NS0 cell cultures. Cytotechnology. 1996;22:239–250. doi: 10.1007/BF00353944. [DOI] [PubMed] [Google Scholar]
  175. Zhou W, Chen C-C, Buckland B, Aunins J. Fed-batch culture of recombinant NS0 myeloma cells with high monoclonal antibody production. Biotechnol Bioeng. 1997;55:783–792. doi: 10.1002/(SICI)1097-0290(19970905)55:5&#x0003c;783::AID-BIT8&#x0003e;3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
  176. Zielke HR, Sumbilla CM, Sevdalian DA, Hawkins RL, Ozand PT. Lactate: a major product of glutamine metabolism by human diploid fibroblasts. J Cell Physiol. 1980;104:433–441. doi: 10.1002/jcp.1041040316. [DOI] [PubMed] [Google Scholar]
  177. Zumla A, McCormack A, George A, Batchelor R, Lechler R. Use of a murine T cell hybridoma expressing human T cell receptor α-gene and β-gene products as a tool for the production of human T cell receptor specific monoclonal antibodies. Human Immunol. 1992;35:141–148. doi: 10.1016/0198-8859(92)90098-8. [DOI] [PubMed] [Google Scholar]

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