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Gene Review

PENK  -  proenkephalin

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Disease relevance of PENK

  • In contrast, increased synthesis of proenkephalin in response to phorbol esters was not affected by pertussis toxin treatment [1].
  • Recombinant PE was obtained by high level expression in Escherichia coli, with the pET3c expression vector; PE was then purified from E. coli by DEAE-Sepharose chromatography, preparative gel electrophoresis, and reverse-phase HPLC [2].

High impact information on PENK


Chemical compound and disease context of PENK


Biological context of PENK


Anatomical context of PENK


Associations of PENK with chemical compounds


Regulatory relationships of PENK


Other interactions of PENK

  • Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to secretory stimuli [22].
  • In contrast, the 70-kDa aspartic proteinase cleaved POMC most readily, with cleavage of proenkephalin and some processing of pro-NPY [23].
  • Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons [16].
  • This study demonstrates that "protease nexin 2 (PN2)," the secreted form of the kunitz protease inhibitor (KPI) of the amyloid precursor protein (APP), potently inhibited the proenkephalin processing enzyme known as prohormone thiol protease (PTP), with a Ki,app of 400 nM [24].
  • The other opioid peptides were [Met]-enkephalyl-Arg6-Phe7 and [Met]-enkephalyl-Arg6-Gly7-Leu8 from proenkephalin; alpha-neoendorphin, beta-neoendorphin, dynorphin A(1-8), dynorphin A(1-17), and dynorphin B from prodynorphin; and [Leu]-enkephalin, which can be derived from either precursor [25].

Analytical, diagnostic and therapeutic context of PENK


  1. Pertussis toxin enhances proenkephalin synthesis in bovine chromaffin cells. Wilson, S.P. J. Neurochem. (1993) [Pubmed]
  2. "Prohormone thiol protease" (PTP) processing of recombinant proenkephalin. Schiller, M.R., Mende-Mueller, L., Moran, K., Meng, M., Miller, K.W., Hook, V.Y. Biochemistry (1995) [Pubmed]
  3. Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla. Seizinger, B.R., Liebisch, D.C., Gramsch, C., Herz, A., Weber, E., Evans, C.J., Esch, F.S., Böhlen, P. Nature (1985) [Pubmed]
  4. Nicotinic receptor stimulation activates enkephalin release and biosynthesis in adrenal chromaffin cells. Eiden, L.E., Giraud, P., Dave, J.R., Hotchkiss, A.J., Affolter, H.U. Nature (1984) [Pubmed]
  5. Presence in brain of synenkephalin, a proenkephalin-immunoreactive protein which does not contain enkephalin. Liston, D.R., Vanderhaeghen, J.J., Rossier, J. Nature (1983) [Pubmed]
  6. Pertussis toxin stimulates the secretion of [Met5]-enkephalin and the expression of proenkephalin A mRNA in bovine adrenal medullary chromaffin cells. Suh, H.H., Hudson, P., McMillian, M.K., Hong, J.S. Biol. Signals (1992) [Pubmed]
  7. Proenkephalin A gene expression in bovine adrenal chromaffin cells is regulated by changes in electrical activity. Kley, N., Loeffler, J.P., Pittius, C.W., Höllt, V. EMBO J. (1986) [Pubmed]
  8. Evidence for the phosphorylation of a proenkephalin-derived peptide, peptide B. D'Souza, N.B., Lindberg, I. J. Biol. Chem. (1988) [Pubmed]
  9. Multiple regulation of proenkephalin gene expression by protein kinase C. Kley, N. J. Biol. Chem. (1988) [Pubmed]
  10. The isolation and chemical characterization of phosphorylated enkephalin-containing peptides from bovine adrenal medulla. Watkinson, A., Young, J., Varro, A., Dockray, G.J. J. Biol. Chem. (1989) [Pubmed]
  11. Processing of proenkephalin is tissue-specific. Liston, D., Patey, G., Rossier, J., Verbanck, P., Vanderhaeghen, J.J. Science (1984) [Pubmed]
  12. Quantitation of proenkephalin A messenger RNA in bovine brain, pituitary and adrenal medulla: correlation between mRNA and peptide levels. Pittius, C.W., Kley, N., Loeffler, J.P., Höllt, V. EMBO J. (1985) [Pubmed]
  13. An investigation of the molecular properties and stability of intermediates of proenkephalin in isolated bovine adrenal medullary chromaffin granules. Birch, N.P., Davies, A.D., Christie, D.L. J. Biol. Chem. (1987) [Pubmed]
  14. A putative processing enzyme for proenkephalin in bovine adrenal chromaffin granule membranes. Purification and properties. Shen, F.S., Roberts, S.F., Lindberg, I. J. Biol. Chem. (1989) [Pubmed]
  15. N-linked glycosylation of a proenkephalin A-derived peptide. Evidence for the glycosylation of an NH2-terminally extended Met-enkephalin Arg6-Gly7-Leu8 variant. Watkinson, A., Dockray, G.J., Young, J. J. Biol. Chem. (1988) [Pubmed]
  16. Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons. Vanderhaeghen, J.J., Lotstra, F., Liston, D.R., Rossier, J. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  17. Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Toneff, T., Bundey, R., Miller, R., Schilling, B., Petermann, I., Dehnert, J., Logvinova, A., Goldsmith, P., Neveu, J.M., Lane, W.S., Gibson, B., Reinheckel, T., Peters, C., Bogyo, M., Hook, V. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  18. Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells. Naranjo, J.R., Mocchetti, I., Schwartz, J.P., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  19. A calcium-initiated signaling pathway propagated through calcineurin and cAMP response element-binding protein activates proenkephalin gene transcription after depolarization. Hahm, S.H., Chen, Y., Vinson, C., Eiden, L.E. Mol. Pharmacol. (2003) [Pubmed]
  20. Processing of proenkephalin in adrenal chromaffin cells. Wilson, S.P. J. Neurochem. (1991) [Pubmed]
  21. Insulin-like growth factor I enhances proenkephalin synthesis and dopamine beta-hydroxylase activity in adrenal chromaffin cells. Wilson, S.P. Life Sci. (1991) [Pubmed]
  22. Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to secretory stimuli. Wan, D.C., Marley, P.D., Livett, B.G. Brain Res. Mol. Brain Res. (1991) [Pubmed]
  23. The processing proteases prohormone thiol protease, PC1/3 and PC2, and 70-kDa aspartic proteinase show preferences among proenkephalin, proneuropeptide Y, and proopiomelanocortin substrates. Hook, V.Y., Schiller, M.R., Azaryan, A.V. Arch. Biochem. Biophys. (1996) [Pubmed]
  24. The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP) inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP). Colocalization of KPI/APP and PTP in secretory vesicles. Hook, V.Y., Sei, C., Yasothornsrikul, S., Toneff, T., Kang, Y.H., Efthimiopoulos, S., Robakis, N.K., Van Nostrand, W. J. Biol. Chem. (1999) [Pubmed]
  25. Distribution pattern of metorphamide compared with other opioid peptides from proenkephalin and prodynorphin in the bovine brain. Sonders, M., Weber, E. J. Neurochem. (1987) [Pubmed]
  26. Molecular cloning establishes proenkephalin as precursor of enkephalin-containing peptides. Gubler, U., Seeburg, P., Hoffman, B.J., Gage, L.P., Udenfriend, S. Nature (1982) [Pubmed]
  27. Isolation and structure of a C-terminally amidated nonopioid peptide, amidorphin-(8-26), from bovine striatum: a major product of proenkephalin in brain but not in adrenal medulla. Liebisch, D.C., Weber, E., Kosicka, B., Gramsch, C., Herz, A., Seizinger, B.R. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  28. Characterization of the molecular forms of proenkephalin in bovine adrenal medulla and rat adrenal, brain, and spinal cord with a site-directed antiserum. Birch, N.P., Christie, D.L. J. Biol. Chem. (1986) [Pubmed]
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