Abstract
It is well established that peptide hormones are synthesized as larger peptide precursors. Initially this was demonstrated by pulse-chase studies, in vitro synthesis, and immunoprecipitation (Docherty and Steiner, 1982; Loh and Gainer, 1983, for reviews), but molecular biology has now made the sequences of a large number of hormone precursors available, for example, proopiomelanocortin (Nakanishi et al., 1979), proenkephalin (Noda et al., 1982), provasopressin (Land et al., 1982), and prooxytocin (Land et al., 1983). These sequences show certain common features (Fig. 1); in particular, the hormone sequences are bracketed by pairs of basic amino acid residues such as Lys-Arg, Lys-Lys, or Arg-Arg. The precursor forms of these hormones generally lack biological activity, so that limited proteolysis at paired basic residues is necessary to generate the hormones, followed by exopeptidase activity to remove the Lys and Arg terminal residues, which are not found in the mature peptide hormones. Carboxypeptidases (Fricker and Snyder, 1983; Hook and Loh, 1984) and aminopeptidases (Gainer et al., 1984) have been described that are capable of such modifications. However, this discussion is confined to the initial proteolysis by endopeptidases. Cleavage may be followed by other modifications such as acetylation and amidation in order to produce biological potency (Loh and Gainer, 1983, for review).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ben-Barak, Y., Russell, J. T., Whitnall, M. H., Ozato, K., and Gainer, H., 1984, Neurophysin in the hypothalamo-neurohypophysial system. I. Production and characterization of monoclonal antibodies, J. Neurosci. 5:81–97.
Chang, T.-L., and Loh, Y. P., 1983, Characterization of proopiocortin converting activity in rat anterior pituitary secretory granules, Endocrinology 112:1832–1839.
Chang, T.-L., and Loh, Y. P., 1984, In vitro processing of proopiocortin by membrane associated and soluble converting enzyme activities from rat intermediate lobe secretory granules, Endocrinology 114:2092–2099.
Chang, T.-L., Gainer, H., Russell, J. T., and Loh, Y. P., 1982, Proopiocortin-converting enzyme activity in bovine neurosecretory granules, Endocrinology 111:1607–1614.
Cromlish, J. A., Seidah, N. G., and Chretien, M. N., 1985, Isolation and characterization of four proteases from porcine pituitary neurointermediate lobes: Relationship to the maturation enzyme of prohormones, Neuropeptides 5:493–496.
Docherty, K., and Steiner, D., 1982, Post-translational proteolysis in polypeptide hormone biosynthesis, Annu. Rev. Physiol. 44:625–638.
Evangelista, R., Ray, P., and Lewis, R. V., 1982, A “trypsin-like” enzyme in adrenal chromaffin granules: A proenkephalin processing enzyme, Biochem. Biophys. Res. Commun. 106:895–902.
Fletcher, D. J., Noe, B. D., Bauer, G. E., and Quigley, J. P., 1980, Characterization of the conversion of a somatostatin precursor to somatostatin by islet secretory granules, Diabetes 29:593–599.
Fletcher, D. J., Noe, B. D., Bauer, G. E., and Quigley, J. P., 1981, Characterization of proinsulin and proglucagon converting activities in isolated islet secretory granules, J. Cell Biol. 90:312–322.
Flicker, L. D., and Snyder, S. H., 1983, Purification and characterization of enkephalin convertase, an enkephalin-synthesizing carboxypeptidase, J. Biol. Chem. 258:1050–1055.
Gainer, H., Same, Y. L., and Brownstein, M. J., 1977, Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides, J. Cell Biol. 73:366–381.
Gainer, H., Russell, J. T., and Loh, Y. P., 1984, An aminopeptidase activity in bovine pituitary secretory vesicles that cleaves the N-terminal arginine from β-lipotropin6o–65, FEBS Lett. 175:135–139.
Gainer, H., Russell, J. T., and Loh, Y. P., 1985, The enzymology and intracellular organization of peptide precursor processing: The secretory vesicle hypothesis, Neuroendocrinology 40:171–184.
Hook, V. Y. H., and Loh, Y. P., 1984, Carbopeptidase B-like converting enzyme activity in secretory granules of rat pituitary, Proc. Natl. Acad. Sci. U.S.A. 81:2776–2780.
Julius, D., Brake, A., Blair, L., Kunisawa, R., and Thomer, J., 1984, Isolation of the putative structural gene for the lysine arginine cleaving endopeptidase required for processing of prepro a factor, Cell 36:1075–1089.
Kemmler, W., Steiner, D. F., and Borg, J., 1973, Studies on the conversion of proinsulin to insulin, J. Biol. Chem. 248:4544–4551.
Kurjan, J., and Herskowitz, I., 1982, Structure of a yeast pheromone gene (MF a) a putative a factor precursor contains four tandem repeats of mature a factor, Cell 30:933–942.
Land, H., Schutz, G., Schmale, H., and Richter, D., 1982, Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor, Nature 295:299–303.
Land, H., Grez, M., Ruppert, S., Schmale, H., Rahbein, M., Richter, D., and Schutz, G., 1983, Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor DNA, Nature 302:342–344.
Lindberg, I., Yang, M.-Y. T., and Costa, E., 1984, Further characterization of an enkephalin-generating enzyme from adrenal-medullary chromaffin granules, J. Neurochem. 42:1411–1419.
Loh, Y. P., and Gainer, H., 1983, Biosynthesis and processing of neuropeptides, in: Brain Peptides (D. Krieger, M. Brownstein, and J. Martin, eds.), John Wiley & Sons, New York, pp. 79–116.
Loh, Y. P., and Gritsch, H. A., 1981, Evidence for intragranular processing of pro-opiocortin in the mouse pituitary intermediate lobe, Eur. J. Cell Biol. 26:177–183.
Loh, Y. P., Tarn, W. H. H., and Russell, J. T., 1984, Measurement of ApH and membrane potential in secretory vesicles isolated from bovine pituitary intermediate lobe, J. Biol. Chem. 259:8238–8245.
Loh, Y. P., Parish, D. C., and Tuteja, R., 1985, Purification and characterization of a paired basic residue-specific proopiomelanocortin converting enzyme from bovine pituitary intermediate lobe vesicles, J. Biol. Chem. 260:7194–7205.
MacGregor, R. R., Chu, L. L. M., and Cohn, D. V., 1976, Conversion of proparathyroid hormone to parathyroid hormone by a paniculate enzyme of the parathyroid gland, J. Biol. Chem. 251:6711–6716.
MacGregor, R. R., Hamilton, J. W., and Cohn, D. V., 1978, The mode of conversion of propara-thormone to parathormone by a particulate converting enzymic activity of the parathyroid gland, J. Biol. Chem. 253:2012–2017.
Mizuno, K., and Matsuo, H., 1984, A novel protease from yeast with specificity towards paired basic residues, Nature 309:558–560.
Mizuno, K., and Matsuo, H., 1985, Proenkephalin processing enzyme with specificity towards paired basic residues purified from bovine adrenal chromaffin granules, Neuropeptides 5:489–492.
Mizuno, K., Kojima, M., and Matsuo, H., 1985, A putative prohormone processing protease in bovine adrenal medulla specifically cleaving in between Lys-Arg sequences, Biochem. Biophys. Res. Comm. 128:884–891.
Nakanishi, S., Ionue, A., Kita, T., Nakamura, M., Chang, A. C. Y., Cohen, S. N., and Numa, S., 1979, Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor, Nature 278:423–427.
Noda, M., Taranishi, Y., Takahashi, H., Toyosato, M., Natake, M., Nakanishi, S., and Numa, S., 1982, Isolation and structural organization of the human preproenkephalin gene, Nature 297:432–434.
Noe, B. D., Debo, G., and Speiss, J., 1984, Comparison of prohormone-processing activities in islet microsomes and secretory granules: Evidence for distinct converting enzymes for separate islet prosomatostatins. J. Cell Biol. 99:578–587.
Pelaprat, D., Sidah, N. G., Sikstrom, R. A., Lambelin, P., Hamelin, J., Lazure, C., Cromlish, J. A., and Chretien, M., 1984, Subcellular fractionation of pituitary neurointermediate lobes: Revelation of various basic proteases, Endocrinology 115:581–590.
Quinn, P. S., and Judah, J. D., 1978, Calcium dependent Golgi-vesicle fusion and cathepsin B in the conversion of proalbumin into albumin in rat liver, Biochem. J. 172:301–309.
Russell, J. T., 1984, ApH, H+ diffusion potentials, and Mg2+ ATPase in neurosecretory vesicles isolated from bovine neurohypophyses, J. Biol. Chem. 259:9496–9507.
Smyth, D. G., Austen, B. M., Bradbury, A. F., Geison, M. J., and Small, C. R., 1977, Biogenesis and metabolism of opiate active peptides, in: Centrally Acting Peptides (J. Hughes, ed.), Macmillan, London, pp. 231–239.
Troy, C. M., and Musacchio, J. M., 1982, Processing of enkephalin precursors by chromaffin granule enzymes, Life Sci. 31:1717–1720.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Parish, D.C. (1986). Prohormone-Converting Enzymes. In: Moody, T.W. (eds) Neural and Endocrine Peptides and Receptors. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5152-8_4
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5152-8_4
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5154-2
Online ISBN: 978-1-4684-5152-8
eBook Packages: Springer Book Archive