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. 1985 Jan;4(1):133–138. doi: 10.1002/j.1460-2075.1985.tb02327.x

Genes for the alpha and gamma subunits of mouse nerve growth factor are contiguous.

B A Evans, R I Richards
PMCID: PMC554161  PMID: 3848399

Abstract

Here we describe the structure and linkage of genes encoding the alpha and gamma subunits of mouse nerve growth factor (NGF). These genes are members of the highly homologous glandular kallikrein multigene family. Together with the beta subunit, the alpha and gamma proteins constitute the high mol. wt. (7S) form of NGF isolated from mouse submandibular gland. The gamma subunit is an active serine protease and is thought to cleave pro-beta-NGF to generate the mature growth factor. The alpha subunit has no detectable proteolytic activity, but is essential for the stable formation of 7S NGF. Lack of enzyme activity of the alpha subunit can be attributed, at least in part, to the deletion of 15 nucleotides in a highly conserved coding region which is normally involved in the activation of serine proteases from their inactive zymogen form.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benoist C., O'Hare K., Breathnach R., Chambon P. The ovalbumin gene-sequence of putative control regions. Nucleic Acids Res. 1980 Jan 11;8(1):127–142. doi: 10.1093/nar/8.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  3. Berger E. A., Shooter E. M. Evidence for pro-beta-nerve growth factor, a biosynthetic precursor to beta-nerve growth factor. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3647–3651. doi: 10.1073/pnas.74.9.3647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bode W. Aktivierung, Aktivität und inhibierung des Rindertrypsins. Naturwissenschaften. 1979 May;66(5):251–258. doi: 10.1007/BF00571605. [DOI] [PubMed] [Google Scholar]
  5. Bode W. The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. II. The binding of the pancreatic trypsin inhibitor and of isoleucine-valine and of sequentially related peptides to trypsinogen and to p-guanidinobenzoate-trypsinogen. J Mol Biol. 1979 Feb 5;127(4):357–374. doi: 10.1016/0022-2836(79)90227-4. [DOI] [PubMed] [Google Scholar]
  6. Bradshaw R. A. Nerve growth factor. Annu Rev Biochem. 1978;47:191–216. doi: 10.1146/annurev.bi.47.070178.001203. [DOI] [PubMed] [Google Scholar]
  7. Corden J., Wasylyk B., Buchwalder A., Sassone-Corsi P., Kedinger C., Chambon P. Promoter sequences of eukaryotic protein-coding genes. Science. 1980 Sep 19;209(4463):1406–1414. doi: 10.1126/science.6251548. [DOI] [PubMed] [Google Scholar]
  8. Enquist L., Sternberg N. In vitro packaging of lambda Dam vectors and their use in cloning DNA fragments. Methods Enzymol. 1979;68:281–298. doi: 10.1016/0076-6879(79)68020-5. [DOI] [PubMed] [Google Scholar]
  9. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  10. Greene L. A., Shooter E. M., Varon S. Enzymatic activities of mouse nerve growth factor and its subunits. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1383–1388. doi: 10.1073/pnas.60.4.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greene L. A., Shooter E. M., Varon S. Subunit interaction and enzymatic activity of mouse 7S nerve growth factor. Biochemistry. 1969 Sep;8(9):3735–3741. doi: 10.1021/bi00837a037. [DOI] [PubMed] [Google Scholar]
  12. Howles P. N., Dickinson D. P., DiCaprio L. L., Woodworth-Gutai M., Gross K. W. Use of a cDNA recombinant for the gamma-subunit of mouse nerve growth factor to localize members of this multigene family near the TAM-1 locus on chromosome 7. Nucleic Acids Res. 1984 Mar 26;12(6):2791–2805. doi: 10.1093/nar/12.6.2791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Isackson P. J., Bradshaw R. A. The alpha-subunit of mouse 7 S nerve growth factor is an inactive serine protease. J Biol Chem. 1984 May 10;259(9):5380–5383. [PubMed] [Google Scholar]
  14. Karin M., Cathala G., Nguyen-Huu M. C. Expression and regulation of a human metallothionein gene carried on an autonomously replicating shuttle vector. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4040–4044. doi: 10.1073/pnas.80.13.4040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  16. Krieger M., Kay L. M., Stroud R. M. Structure and specific binding of trypsin: comparison of inhibited derivatives and a model for substrate binding. J Mol Biol. 1974 Feb 25;83(2):209–230. doi: 10.1016/0022-2836(74)90388-x. [DOI] [PubMed] [Google Scholar]
  17. Mason A. J., Evans B. A., Cox D. R., Shine J., Richards R. I. Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature. 1983 May 26;303(5915):300–307. doi: 10.1038/303300a0. [DOI] [PubMed] [Google Scholar]
  18. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  19. Poe M., Wu J. K., Florance J. R., Rodkey J. A., Bennett C. D., Hoogsteen K. Purification and properties of renin and gamma-renin from the mouse submaxillary gland. J Biol Chem. 1983 Feb 25;258(4):2209–2216. [PubMed] [Google Scholar]
  20. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  21. Richards R. I., Catanzaro D. F., Mason A. J., Morris B. J., Baxter J. D., Shine J. Mouse glandular kallikrein genes. Nucleotide sequence of cloned cDNA coding for a member of the kallikrein arginyl esteropeptidase group of serine proteases. J Biol Chem. 1982 Mar 25;257(6):2758–2761. [PubMed] [Google Scholar]
  22. Richards R. I., Heguy A., Karin M. Structural and functional analysis of the human metallothionein-IA gene: differential induction by metal ions and glucocorticoids. Cell. 1984 May;37(1):263–272. doi: 10.1016/0092-8674(84)90322-2. [DOI] [PubMed] [Google Scholar]
  23. Ronne H., Anundi H., Rask L., Peterson P. A. 7S Nerve growth factor alpha and gamma subunits are closely related proteins. Biochemistry. 1984 Mar 13;23(6):1229–1234. doi: 10.1021/bi00301a032. [DOI] [PubMed] [Google Scholar]
  24. Ronne H., Lundgren S., Severinsson L., Rask L., Peterson P. A. Growth factor-binding proteases in the murine submaxillary gland: isolation of a cDNA clone. EMBO J. 1983;2(9):1561–1564. doi: 10.1002/j.1460-2075.1983.tb01624.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Scott J., Selby M., Urdea M., Quiroga M., Bell G. I., Rutter W. J. Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor. Nature. 1983 Apr 7;302(5908):538–540. doi: 10.1038/302538a0. [DOI] [PubMed] [Google Scholar]
  27. Silverman R. E., Bradshaw R. A. Nerve growth factor: subunit interactions in the mouse submaxillary gland 7S complex. J Neurosci Res. 1982;8(2-3):127–136. doi: 10.1002/jnr.490080204. [DOI] [PubMed] [Google Scholar]
  28. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  29. Swift G. H., Dagorn J. C., Ashley P. L., Cummings S. W., MacDonald R. J. Rat pancreatic kallikrein mRNA: nucleotide sequence and amino acid sequence of the encoded preproenzyme. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7263–7267. doi: 10.1073/pnas.79.23.7263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thomas K. A., Baglan N. C., Bradshaw R. A. The amino acid sequence of the gamma-subunit of mouse submaxillary gland 7 S nerve growth factor. J Biol Chem. 1981 Sep 10;256(17):9156–9166. [PubMed] [Google Scholar]
  31. Tschesche H., Mair G., Godec G. The primary structure of porcine glandular kallikreins. Adv Exp Med Biol. 1979;120A:245–260. doi: 10.1007/978-1-4757-0926-1_25. [DOI] [PubMed] [Google Scholar]
  32. Ullrich A., Gray A., Berman C., Dull T. J. Human beta-nerve growth factor gene sequence highly homologous to that of mouse. Nature. 1983 Jun 30;303(5920):821–825. doi: 10.1038/303821a0. [DOI] [PubMed] [Google Scholar]
  33. Varon S., Normura J., Shooter E. M. Reversible dissociation of the mouse nerve growth factor protein into different subunits. Biochemistry. 1968 Apr;7(4):1296–1303. doi: 10.1021/bi00844a008. [DOI] [PubMed] [Google Scholar]
  34. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  35. Yankner B. A., Shooter E. M. The biology and mechanism of action of nerve growth factor. Annu Rev Biochem. 1982;51:845–868. doi: 10.1146/annurev.bi.51.070182.004213. [DOI] [PubMed] [Google Scholar]

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