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Identification of Neurotrophic Factors by Molecular Biological Techniques

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Part of the book series: Neuromethods ((NM,volume 25))

Abstract

Many proteins have “neurotrophic” activities in in vitro or in vivo test systems. Originally these were discovered as certain neurotrophic activities with unknown molecular structures. Nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) were discovered by their specific neurotrophic properties. They were purified from tissue extracts using in vitro bioassays based on the survival of specific nerve cells and subsequently all or part of their primary protein sequences were determined. Other proteins, such as the insulin-like growth factors (IGFs), the fibroblast growth factors (FGFs), epidermal growth factor (EGF), and S100β, were originally discovered based on nonneurotrophic activities and they were later found to act as neurotrophic agents on certain types of nerve cells. All of these factors were initially discovered, isolated, and purified based on their respective bioactivities and then their primary structures.

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References

  • Angeletti R. H. and Bradshaw R. A. (1971) Nerve growth factor from mouse submaxillary gland, amino acid sequence. Proc. Natl. Acad. Sci. USA 68, 2417–2420

    Article  PubMed  CAS  Google Scholar 

  • Angeletli R. H., Mercanti D., and Bradshaw R. A. (1973a) Ammo acid sequences of mouse 2.5S nerve growth factor. I. Biochemrstry 12, 90–100.

    Article  Google Scholar 

  • Angeletti R. H., Hermodson M. A., and Bradshaw R. A. (1973b) Ammo acid sequences of mouse 2.5S nerve growth factor. II. Isolation and characterization of the thermolytic and peptic peptides and the complete covalent structure. Biochemisty 12, 100–115.

    Article  CAS  Google Scholar 

  • Barde Y.-A. (1989) Trophic factors and neuronal survival. Neuron 2, 1525–1534.

    Article  PubMed  CAS  Google Scholar 

  • Barde Y.-A., Edgar D., and Thoenen H. (1982) Puriflcatron of a new neurotrophic factor from mammalian brain. EMBO J. 1, 549–553.

    PubMed  CAS  Google Scholar 

  • Beck C. E. and Perez-Polo J. R. (1982) Human beta-nerve growth factor does not cross react with antibodies to mouse beta-nerve growth factor in a two-site radiounmunoassay. J. Neurosa. Res. 8, 137–152.

    Article  CAS  Google Scholar 

  • Berkemeier L. R., Winslow J. W., Kaplan D. R., Nikolics K., Goeddel D. V., and Rosenthal A. R. (1991) Neurotrophin-5, a novel neurotrophic factor that activates trk and trkB. Neuron 7, 857–866.

    Article  PubMed  CAS  Google Scholar 

  • Bocchini V. and Angeletti P. U. (1969) The nerve growth factor: purification as a 30,000 molecular weight protein. Proc. NutI. Acad. Sci. USA 64, 787.

    Article  CAS  Google Scholar 

  • Borsani G., Pizzuti A., Rugarli E. I., Falini A., Silani V., Sidoli A., Scarlato G., and Baralle F. E. (1990) cDNA sequence of human /gb-NGF. Nucl. Acids Res. 18, 4020.

    Article  PubMed  CAS  Google Scholar 

  • Bueker E. D. (1948) Implantation of tumors in the hind limb field of the embryonic chick and the developmental response of the lumbosacral nervous system. Amt. Rec. 102, 369–390.

    CAS  Google Scholar 

  • Carriero F., Campioni N. Cardinali B., and Pierandrei-Amaldi P. (1991) Structure and expression of the nerve growth factor gene in Xenopus oocytes and embryos. Mol. Reprod. Dev. 29, 313–322.

    Article  PubMed  CAS  Google Scholar 

  • Cohn S. (1960) Purification of a nerve growth-promoting protein from the mouse salivary gland and its neurocytotoxic antiserum. Pm. Nutl. Acud. Sci. USA 45, 302–311.

    Article  Google Scholar 

  • Ebendal T., Larhammar D., and Persson H. (1986) Structure and expression of the chicken beta nerve growth factor gene. EMBO J. 5, 1483–1487.

    PubMed  CAS  Google Scholar 

  • Edwards R. H., Selby M. J., and Rutter W. J. (1986) Differential RNA splicing predicts two distinct nerve growth factor precursors. Nature 319, 784–787.

    Article  PubMed  CAS  Google Scholar 

  • Ernfors P., Ibanez C. F., Ebendal T., Olson L., and Persson H. (1990) Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor, developmental and topographical expression in the brain. proc. Natl. Acad. Sci. USA 87, 5454–5458.

    Article  PubMed  CAS  Google Scholar 

  • Fahnestock M. and Bell R. A. (1990) Molecular cloning of a cDNA encoding the nerve growth factor precursor from Mastomys natalems. Gene 69, 257–264.

    Google Scholar 

  • Goldstem L. D., Reynolds C. P., and Perez-Polo J R. (1978) Isolation of human nerve growth factor from placental tissue. Neurochem.Res. 3, 185–193.

    Article  Google Scholar 

  • Hallboök F., Ibañez C. F., and Persson H. (1991) Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed III Xenopus ovary. Neuron 6, 845–858.

    Article  PubMed  Google Scholar 

  • Hohn A., Leibrock J., Bailey K., and Barde Y. A. (1990) Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature 344, 339–341.

    Article  PubMed  CAS  Google Scholar 

  • Isacson P. J., Towner M. D., and Huntsman M. M. (1991) Comparison of mammalian chicken and Xenopus bram-derived neurotrophic factor coding sequences. FEBS Lett. 285, 260–264.

    Article  Google Scholar 

  • Jones K. R. and Reichardt L. F. (1990) Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc. Natl. Acad. Sci USA. 87, 8060–8064.

    Article  PubMed  CAS  Google Scholar 

  • Kaisho Y., Yoshimura K., and Nakahama K. (1990) Cloning and expression of a cDNA encoding a novel human neurotrophic factor. FEBS Lett. 266, 187–191.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan D. R., Hempstead B. L., Martm-Zanca D., Chao M. V., and Parada L. F. (1991) The trk proto-oncogene product, a signal transducing receptor for nerve growth factor. Science 252, 554–560.

    Article  PubMed  CAS  Google Scholar 

  • Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., and Barde Y. A. (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341, 149–152.

    Article  PubMed  CAS  Google Scholar 

  • Levi-Montalciru R. (1987) The nerve growth factor thirty-five years later. In Vitro Cell. Dev. Biol. 23, 227–238.

    Article  Google Scholar 

  • Macklin W. B. and Campagnoni C. W. (1990) Neuromethods 16 Molecular Neurobiological Technzques (Boulton A. A., Baker G. A., and Campagnoni A. T., eds.), Humana Press, Totowa, NJ, pp. 117–152.

    Google Scholar 

  • Maisonpierre P. G, Belluscio L., Squinto S., Ip N. Y,, Furth M. E., Lindsay R. M., and Yancopoulos G. D. (1990) Neurotrophin-3, a neurotrophic factor related to NGF and BDNF. Science., 247, 1446–1451.

    Article  PubMed  CAS  Google Scholar 

  • McDonald N. Q., Lapatto R., Murray-Rust J., Gunning J., Wlodawer A., and Blundell T. L. (1991) New protein fold revealed by a 2.3-Å resolution crystal structure of nerve growth factor. Nature 354, 411–414.

    Article  PubMed  CAS  Google Scholar 

  • Meier R., Becker-Andre M, Götz R., Heumann R., Shaw A., and Thoenen H. (1986) Molecular cloning of bovine and chick nerve growth factor (NGF), delineatron of conserved and unconserved domains and their relationship to the biological activity and antigenicity of NGF. EMBO J. 5, 1489–1493.

    PubMed  CAS  Google Scholar 

  • Miyajima A., Miyatake S., Schreurs J., DeVries J., Arai N., Yokota T., and Arai K. (1988) Coordinate regulation of immune and inflammatory responses by T cell derived lymphokines. FASEB J. 2, 2462–2473.

    PubMed  CAS  Google Scholar 

  • Murphy R A., Chlumecky V., Smillie L. B., Carpenter M., Nattriss M., Anderson J. K., Rhodes J. A., Barker P. A., Siminoski K., Campenot R. B., and Haskins J. (1989) Isolation and characterization of a glycosylated form of β nerve growth factor in mouse submandibular glands. J. Biul. Chem. 264, 12,502–12,509.

    CAS  Google Scholar 

  • Newman S. and Campagnoni A. T. (1990) Neuromethods 16: Molecular Neurobiologicul Techniques (Boulton A. A., Baker G. A., and Campagnoni A. T., eds.), Humana Press, Totowa, NJ, pp. 13–48

    Google Scholar 

  • Rosenthal A., Goeddel D.V., Nguyen T., Lewis M., Shih A., Laramee G. R., Nikohcs K., and Winslow J. W. (1990) Primary structure and biological activity of a novel human neurotrophic factor. Neuron 4, 767–773.

    Article  PubMed  CAS  Google Scholar 

  • Schwarz M. A., Fisher D., Bradshaw R. A., and Isa&son P. J., (1989) Isolation and sequence of a cDNA clone of β-vnerve growth factor from the guinea pig prostate gland. J, Neurochem. 52, 1203–1209.

    Article  CAS  Google Scholar 

  • Scott J., Selby M., Urdea M., Quiroga M., Bell G I., and Rutter W. J. (1983) Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor. Nature 302, 538–540.

    Article  PubMed  CAS  Google Scholar 

  • Selby M. J., Edwards R., Sharp F., and Rutter W. J. (1987a) Mouse nerve growth factor gene, structure and expression. Mol. Cell. Biol. 7, 3057–3064.

    PubMed  CAS  Google Scholar 

  • Selby M. J., Edwards R., Sharp F., and Rutter W. J. (1987a) Cobra nerve growth factor, structure and evolutionary comparison. J, Neurosci. Res. 18, 293–298.

    Article  CAS  Google Scholar 

  • Soppet D., Escandon E., Maragos J., Middlemas D. S., Reid S. W., Blair J., Burton L. E., Stanton B. R., Kaplan D. R., Hunter T., Nikolics K., and Parada L. F. (1991) The neurotrophic factors brain-derived neurotrophic factor and neurotrophm-3 are ligands for the trkB tyrosine kinase receptor. Cell 65, 895–903.

    Article  PubMed  CAS  Google Scholar 

  • Ullrich A., Gray A., Berman C., and Dull T. J. (1983) Human beta-nerve growth factor gene sequence highly homologous to that of mouse. Nature 303, 821–825.

    Article  PubMed  CAS  Google Scholar 

  • VonHeijne G. (1986) A new method for predicting signal sequence cleavage sites. Nucl. Acids Res. 14, 683–690.

    Google Scholar 

  • Whittemore S. R., Ebendal T., Larkfors L., Olson L., Seiger A., Stromberg I., and Persson H. (1986) Developmental and regional expression of /gb nerve growth factor messenger RNA and protein in the rat central nervous system. Proc. Nafl. Acad. Sci. USA 83, 817–821.

    Article  CAS  Google Scholar 

  • Wion D., Perret C., Freichin N., Keller A., Behar G., Brachet P., and Auffray C. (1986) Molecular cloning of the avian β-nerve growth factor gene, transcription in the brain. FEBS Lett. 14, 82–86.

    Article  Google Scholar 

  • Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., and Wong G. G. (1986) Human IL-3 (multi-CSF), identification by expression cloning of a novel hematopoietic growth factor related to murme IL-3. Cell 47, 3–10.

    Article  PubMed  CAS  Google Scholar 

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© 1993 Humana Press Inc.

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Nikolics, K. (1993). Identification of Neurotrophic Factors by Molecular Biological Techniques. In: Boulton, A.A., Baker, G.B., Hefti, F. (eds) Neurotrophic Factors. Neuromethods, vol 25. Humana Press, Totowa, NJ. https://doi.org/10.1385/0-89603-249-3:25

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  • DOI: https://doi.org/10.1385/0-89603-249-3:25

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-249-1

  • Online ISBN: 978-1-59259-630-0

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