proprotein convertase 2

Summary

Summary: A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.

Top Publications

  1. Furuta M, Yano H, Zhou A, Rouille Y, Holst J, Carroll R, et al. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc Natl Acad Sci U S A. 1997;94:6646-51 pubmed
    ..SPC2-defective mice offer many possibilities for further delineating neuroendocrine precursor processing mechanisms and for exploring more fully the physiological roles of many neuropeptides and peptide hormones. ..
  2. Benjannet S, Savaria D, Chretien M, Seidah N. 7B2 is a specific intracellular binding protein of the prohormone convertase PC2. J Neurochem. 1995;64:2303-11 pubmed
    ..Coexpression of 7B2 and PC2, although resulting in an elevation of the level of pro-PC2, did not eliminate the processing of pro-PC2 to PC2.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Matthews G, Shennan K, Seal A, Taylor N, Colman A, Docherty K. Autocatalytic maturation of the prohormone convertase PC2. J Biol Chem. 1994;269:588-92 pubmed
    ..The results also demonstrate that the novel Xenopus egg extract translation/translocation system represents a powerful cell-free method for studying proteolytic processing of propolypeptides. ..
  4. Benjannet S, Reudelhuber T, Mercure C, Rondeau N, Chretien M, Seidah N. Proprotein conversion is determined by a multiplicity of factors including convertase processing, substrate specificity, and intracellular environment. Cell type-specific processing of human prorenin by the convertase PC1. J Biol Chem. 1992;267:11417-23 pubmed
    ..Our data demonstrate that propeptide removal from these enzymes, possibly leading to their activation, is not the only criterion which governs precursor processing. ..
  5. Smeekens S, Montag A, Thomas G, Albiges Rizo C, Carroll R, Benig M, et al. Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3. Proc Natl Acad Sci U S A. 1992;89:8822-6 pubmed
    ..These results along with data presented on the expression of both PC2 and PC3 in islet beta cells strongly support the conclusion that these proteases are involved in the conversion of proinsulin to insulin in vivo. ..
  6. Schiller M, Raghunath M, Kubitscheck U, Scholzen T, Fisbeck T, Metze D, et al. Human dermal fibroblasts express prohormone convertases 1 and 2 and produce proopiomelanocortin-derived peptides. J Invest Dermatol. 2001;117:227-35 pubmed
    ..Production of proopiomelanocortin peptides by human dermal fibroblasts may be relevant for fibroblast functions such as collagen degradation and/or regulation of dermal immune responses. ..
  7. Cornwall G, Cameron A, Lindberg I, Hardy D, Cormier N, Hsia N. The cystatin-related epididymal spermatogenic protein inhibits the serine protease prohormone convertase 2. Endocrinology. 2003;144:901-8 pubmed
    ..These studies suggest that CRES is a cross-class inhibitor that may regulate proprotein processing within the reproductive and neuroendocrine systems. ..
  8. Apletalina E, Appel J, Lamango N, Houghten R, Lindberg I. Identification of inhibitors of prohormone convertases 1 and 2 using a peptide combinatorial library. J Biol Chem. 1998;273:26589-95 pubmed
  9. Day R, Lazure C, Basak A, Boudreault A, Limperis P, Dong W, et al. Prodynorphin processing by proprotein convertase 2. Cleavage at single basic residues and enhanced processing in the presence of carboxypeptidase activity. J Biol Chem. 1998;273:829-36 pubmed
    ..Our data suggest that carboxypeptidase activity enhances PC2 processing by the elimination of product inhibition caused by basic residue-extended peptides. ..

More Information

Publications88

  1. Muller L, Zhu X, Lindberg I. Mechanism of the facilitation of PC2 maturation by 7B2: involvement in ProPC2 transport and activation but not folding. J Cell Biol. 1997;139:625-38 pubmed
    ..We propose, therefore, that 7B2 stabilizes proPC2 in a conformation already competent for these two events. ..
  2. Kowalska D, Liu J, Appel J, Ozawa A, Nefzi A, Mackin R, et al. Synthetic small-molecule prohormone convertase 2 inhibitors. Mol Pharmacol. 2009;75:617-25 pubmed publisher
  3. Benjannet S, Rondeau N, Paquet L, Boudreault A, Lazure C, Chretien M, et al. Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 . Biochem J. 1993;294 ( Pt 3):735-43 pubmed
    ..In order to test the possibility that zymogen processing is performed by furin, we co-expressed this convertase with either pro-PC1 or pro-PC2. The data demonstrated the inability of furin to cleave either proenzyme. ..
  4. Mains R, Milgram S, Keutmann H, Eipper B. The NH2-terminal proregion of peptidylglycine alpha-amidating monooxygenase facilitates the secretion of soluble proteins. Mol Endocrinol. 1995;9:3-13 pubmed
    ..In both AtT-20 cells and hEK-293 cells, the PAM/PC2 fusion molecule was able to exit the endoplasmic reticulum more rapidly than PC2. ..
  5. Seidah N, Gaspar L, Mion P, Marcinkiewicz M, Mbikay M, Chretien M. cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases. DNA Cell Biol. 1990;9:415-24 pubmed
    ..8 kb) demonstrated tissue and cellular specificity of expression, only within endocrine and neuroendocrine cells. These data suggest that mPC1 and mPC2 represent prime candidates for tissue-specific pro-hormone converting proteinases. ..
  6. Sarac M, Windeatt S, Castro M, Lindberg I. Intrapituitary adenoviral administration of 7B2 can extend life span and reverse endocrinological deficiencies in 7B2 null mice. Endocrinology. 2002;143:2314-23 pubmed
    ..These data showing partial rescue of 7B2 nulls support the idea that adenoviral administration of 7B2 will represent an effective means to study the role of this interesting neuroendocrine protein on endocrine function in vivo. ..
  7. Ogiwara K, Shinohara M, Takahashi T. Expression of proprotein convertase 2 mRNA in the ovarian follicles of the medaka, Oryzias latipes. Gene. 2004;337:79-89 pubmed
    ..In the present study, a cDNA for proprotein convertase 2 (PC2) was cloned for the first time from a fish...
  8. Schmidt G, Sirois F, Anini Y, Kauri L, Gyamera Acheampong C, Fleck E, et al. Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus (Sgne1). Diabetes. 2006;55:452-9 pubmed
    ..Differential expression of 7B2 may contribute to the difference between B6 and C3H mice not only in glucagon production and secretion but also in glucose tolerance. ..
  9. Jacob T, Kaplan J. The EGL-21 carboxypeptidase E facilitates acetylcholine release at Caenorhabditis elegans neuromuscular junctions. J Neurosci. 2003;23:2122-30 pubmed
    ..Taken together, these results suggest that egl-21 CPE and egl-3 PC2 process endogenous neuropeptides that facilitate acetylcholine release at C. elegans NMJs. ..
  10. Westphal C, Muller L, Zhou A, Zhu X, Bonner Weir S, Schambelan M, et al. The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease. Cell. 1999;96:689-700 pubmed
    ..We conclude that 7B2 is indeed required for activation of PC2 in vivo but has additional important functions in regulating pituitary hormone secretion. ..
  11. Smeekens S, Avruch A, LaMendola J, Chan S, Steiner D. Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans. Proc Natl Acad Sci U S A. 1991;88:340-4 pubmed
    ..These and other differences suggest that these proteins carry out compartmentalized proteolysis within cells, such as processing within regulated versus constitutive secretory pathways. ..
  12. Rouille Y, Bianchi M, Irminger J, Halban P. Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon. FEBS Lett. 1997;413:119-23 pubmed
    ..It is concluded that PC2 is able to act alone in the pancreatic pathway of proglucagon processing. ..
  13. Hörsch D, Day R, Seidah N, Weihe E, Schafer M. Immunohistochemical localization of the pro-peptide processing enzymes PC1/PC3 and PC2 in the human anal canal. Peptides. 1997;18:755-60 pubmed
  14. Hu Z, Pym E, Babu K, Vashlishan Murray A, Kaplan J. A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron. 2011;71:92-102 pubmed publisher
    ..Collectively, these results suggest that NLP-12 mediates a mechanosensory feedback loop that couples muscle contraction to changes in presynaptic release, thereby providing a mechanism for proprioceptive control of locomotion...
  15. Braks J, Martens G. 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell. 1994;78:263-73 pubmed
    ..Our results suggest that 7B2 is a novel type of molecular chaperone preventing premature activation of proPC2 in the regulated secretory pathway. ..
  16. Laurent V, Kimble A, Peng B, Zhu P, Pintar J, Steiner D, et al. Mortality in 7B2 null mice can be rescued by adrenalectomy: involvement of dopamine in ACTH hypersecretion. Proc Natl Acad Sci U S A. 2002;99:3087-92 pubmed
    ..Interestingly, adrenalectomized 7B2 nulls also developed unexpectedly severe obesity. ..
  17. Kass J, Jacob T, Kim P, Kaplan J. The EGL-3 proprotein convertase regulates mechanosensory responses of Caenorhabditis elegans. J Neurosci. 2001;21:9265-72 pubmed
    ..Taken together, these results suggest that egl-3 PC2-processed peptides normally regulate the responsiveness of C. elegans to mechanical stimuli. ..
  18. Li Q, Naqvi S, Shen X, Liu Y, Lindberg I, Friedman T. Prohormone convertase 2 enzymatic activity and its regulation in neuro-endocrine cells and tissues. Regul Pept. 2003;110:197-205 pubmed
    ..PC2 enzymatic activity and PC2 mRNA levels were somewhat discordant suggesting that PC2 mRNA levels do not always reflect PC2 enzymatic activity. ..
  19. Deftos L, Burton D, Hastings R, Terkeltaub R, Hook V. Comparative tissue distribution of the processing enzymes "prohormone thiol protease," and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues. Endocrine. 2001;15:217-24 pubmed
    ..These results support the importance of these processing enzymes in their hypothesized roles in prohormone processing. ..
  20. Berman Y, Mzhavia N, Polonskaia A, Devi L. Impaired prohormone convertases in Cpe(fat)/Cpe(fat) mice. J Biol Chem. 2001;276:1466-73 pubmed
  21. Husson S, Clynen E, Baggerman G, Janssen T, Schoofs L. Defective processing of neuropeptide precursors in Caenorhabditis elegans lacking proprotein convertase 2 (KPC-2/EGL-3): mutant analysis by mass spectrometry. J Neurochem. 2006;98:1999-2012 pubmed
    ..This differential peptidomic approach unambiguously provides evidence for the role of PC2/EGL-3 in the processing of FMRFamide-like peptide (FLP) precursors and neuropeptide-like protein (NLP) precursors in nematodes. ..
  22. Lee S, Lindberg I. 7B2 prevents unfolding and aggregation of prohormone convertase 2. Endocrinology. 2008;149:4116-27 pubmed publisher
    ..Because 7B2 expression is not confined to areas expressing pro-PC2, 7B2 may represent a general intracellular and extracellular secretory chaperone. ..
  23. Martens G, Braks J, Eib D, Zhou Y, Lindberg I. The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2. Proc Natl Acad Sci U S A. 1994;91:5784-7 pubmed
    ..Our findings indicate that 7B2 is a physiological inhibitor of PC2 and may provide alternative avenues for the manipulation of peptide hormone levels. ..
  24. Breslin M, Lindberg I, Benjannet S, Mathis J, Lazure C, Seidah N. Differential processing of proenkephalin by prohormone convertases 1(3) and 2 and furin. J Biol Chem. 1993;268:27084-93 pubmed
  25. Morash M, MacDonald A, Croll R, Anini Y. Molecular cloning, ontogeny and tissue distribution of zebrafish (Danio rerio) prohormone convertases: pcsk1 and pcsk2. Gen Comp Endocrinol. 2009;162:179-87 pubmed publisher
    ..For the first time, we have identified and characterized a pcsk1 transcript in fish. We have also identified and characterized the pcsk2 transcript in zebrafish, and have assessed the tissue distribution and ontogeny of both. ..
  26. Assadi M, Sharpe J, Snell C, Loh Y. The C-terminus of prohormone convertase 2 is sufficient and necessary for Raft association and sorting to the regulated secretory pathway. Biochemistry. 2004;43:7798-807 pubmed
    ..These results showed that the PC2 C-terminus confers raft association and is sufficient and necessary for sorting PC2 to the RSP. ..
  27. Farber C, Chitwood J, Lee S, Verdugo R, Islas Trejo A, Rincon G, et al. Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice. BMC Genet. 2008;9:34 pubmed publisher
    ..The identification of novel genes is critical to understanding the molecular basis of body weight. Towards this goal, we have identified secretogranin V (Scg5; also referred to as Sgne1), as a candidate gene for growth traits...
  28. Rohatgi N, Aly H, Marshall C, McDonald W, Kletzien R, Colca J, et al. Novel insulin sensitizer modulates nutrient sensing pathways and maintains ?-cell phenotype in human islets. PLoS ONE. 2013;8:e62012 pubmed publisher
  29. Tatsumi K, Tanaka S, Takano T, Tahara S, Murakami Y, Takao T, et al. Frequent appearance of autoantibodies against prohormone convertase 1/3 and neuroendocrine protein 7B2 in patients with nonfunctioning pituitary macroadenoma. Endocrine. 2003;22:335-40 pubmed
    ..These results suggest that autoantibodies against PC1/3 and 7B2 are novel tumor-associated autoantibodies and can be helpful in the diagnosis of clinically nonfunctioning pituitary macroadenoma. ..
  30. Tein K, Kasvandik S, Kõks S, Vasar E, Terasmaa A. Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice. Front Mol Neurosci. 2015;8:45 pubmed publisher
    ..Our results suggest a functional link between Wfs1 and PC2. Thus, the detailed molecular mechanism of the role of Wfs1 in the regulation of PC2 activity needs further investigation. ..
  31. Zhang J, Zhou D, You J, Tang B, Li P, Tang S. Differential processing of neuropeptide proprotein in human breast adenocarcinoma. J Endocrinol Invest. 2013;36:745-52 pubmed publisher
    ..The latter may contribute to cancer progression. ..
  32. Dong F, Ma L, Chretien M, Mbikay M. Proteomic analysis of neuroendocrine peptidergic system disruption using the AtT20 pituitary cell line as a model. Methods Mol Biol. 2008;410:111-22 pubmed
    ..Mass spectrometric analysis of tryptic peptides identified two proteins found in more abundance in these cells as proSAAS and Ephrin type A receptor 2. ..
  33. Villeneuve P, Feliciangeli S, Croissandeau G, Seidah N, Mbikay M, Kitabgi P, et al. Altered processing of the neurotensin/neuromedin N precursor in PC2 knock down mice: a biochemical and immunohistochemical study. J Neurochem. 2002;82:783-93 pubmed
    ..However, there was no change in the maturation of pro-NT/NN in the brain of mice in which the PC1 gene had been partially inactivated, implying that complete PC1 knock down may be required for loss of function. ..
  34. Hakes D, Birch N, Mezey A, Dixon J. Isolation of two complementary deoxyribonucleic acid clones from a rat insulinoma cell line based on similarities to Kex2 and furin sequences and the specific localization of each transcript to endocrine and neuroendocrine tissues in rats. Endocrinology. 1991;129:3053-63 pubmed
    ..Probes specific for the mRNAs of each protein were used to localize the expression of each protein in endocrine and neuroendocrine tissues. ..
  35. Dittie A, Tooze S. Characterization of the endopeptidase PC2 activity towards secretogranin II in stably transfected PC12 cells. Biochem J. 1995;310 ( Pt 3):777-87 pubmed
    ..Our results demonstrate that SgII is proteolytically processed by PC2 in the immature secretory granule into several lower-molecular-mass proteins, the major ones being an 18 kDa sulphated fragment and a 28 kDa fragment. ..
  36. Nillni E, Aird F, Seidah N, Todd R, Koenig J. PreproTRH(178-199) and two novel peptides (pFQ7 and pSE14) derived from its processing, which are produced in the paraventricular nucleus of the rat hypothalamus, are regulated during suckling. Endocrinology. 2001;142:896-906 pubmed
    ..These data provide the first evidence for alterations in proTRH processing in the PVN during lactation and suggest that the products of this altered processing may play a physiological role in the regulation of PRL secretion. ..
  37. Erkut Z, Gabreëls B, Eikelenboom J, Van Leeuwen F, Swaab D. Glucocorticoid treatment is associated with decreased expression of processed AVP but not of proAVP, neurophysin or oxytocin in the human hypothalamus: are PC1 and PC2 involved?. Neuro Endocrinol Lett. 2002;23:33-44 pubmed
    ..We conclude that the suppression of AVP expression by GCs is not mediated solely by the down regulation of PC1, PC2 or 7B2. Other mechanisms, which may contribute to the GC-induced posttranslational suppression of AVP, are discussed. ..
  38. Bailyes E, Shennan K, Usac E, Arden S, Guest P, Docherty K, et al. Differences between the catalytic properties of recombinant human PC2 and endogenous rat PC2. Biochem J. 1995;309 ( Pt 2):587-94 pubmed
    ..A modulating effect of carbohydrate on enzyme activity could not be excluded. ..
  39. Minokadeh A, Funkelstein L, Toneff T, Hwang S, Beinfeld M, Reinheckel T, et al. Cathepsin L participates in dynorphin production in brain cortex, illustrated by protease gene knockout and expression. Mol Cell Neurosci. 2010;43:98-107 pubmed publisher
    ..Overall, these results demonstrate a prominent role for cathepsin L, jointly with PC1/3 and PC2, for production of dynorphins in brain. ..
  40. Rehfeld J, Bundgaard J, Hannibal J, Zhu X, Norrbom C, Steiner D, et al. The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6. Endocrinology. 2008;149:1600-8 pubmed
    ..The results suggest that the different peptide patterns in the brain and the gut are due to different expression of PCs. ..
  41. Reynolds N, Blum A, Kitagawa K, Beinfeld M. Inhibition of PC5 expression decreases CCK secretion and increases PC2 expression. Peptides. 2006;27:901-4 pubmed
    ..The decrease in CCK in the media was due largely to loss of CCK 22. These results provide the first direct evidence that PC5 is involved in CCK processing. ..
  42. Webb G, Akbar M, Zhao C, Swift H, Steiner D. Glucagon replacement via micro-osmotic pump corrects hypoglycemia and alpha-cell hyperplasia in prohormone convertase 2 knockout mice. Diabetes. 2002;51:398-405 pubmed
  43. Andersson A, Börjesson A, Sandgren J, Sandler S. Cytokines affect PDX-1 expression, insulin and proinsulin secretion from iNOS deficient murine islets. Mol Cell Endocrinol. 2005;240:50-7 pubmed
    ..PDX-1 mRNA expression was suppressed independent of NO-formation. We conclude that cytokines induce both NO-dependent and NO-independent functional inhibition of murine beta-cells. ..
  44. Suzuki S, Solberg L, Redei E, Handa R. Prepro-thyrotropin releasing hormone 178-199 immunoreactivity is altered in the hypothalamus of the Wistar-Kyoto strain of rat. Brain Res. 2001;913:224-33 pubmed
    ..Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior. ..
  45. Ciesla W. Can melatonin regulate the expression of prohormone convertase 1 and 2 genes via monomeric and dimeric forms of RZR/ROR nuclear receptor, and can melatonin influence the processes of embryogenesis or carcinogenesis by disturbing the proportion of cAM. Med Hypotheses. 2001;56:181-93 pubmed
    ..This method might also be considerably useful in monitoring a safe substitutional hormonotherapy. ..
  46. Dai X, Perez P, Soria G, Scarinci N, Smoler M, Morsucci D, et al. External Ca2+ regulates polycystin-2 (TRPP2) cation currents in LLC-PK1 renal epithelial cells. Exp Cell Res. 2017;350:50-61 pubmed publisher
    ..The data support a novel Ca2+ sensing mechanism for PC2 expression and functional regulation in renal epithelial cells. ..
  47. Yang Y, Ehrlich B. Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2. J Physiol. 2016;594:4141-9 pubmed publisher
    ..Here, we review previous studies that connect the molecular properties of the domains of PC2 Cterm to distinct aspects of PC2 functions and regulation. ..
  48. Cyr N, Stuart R, Zhu X, Steiner D, Nillni E. Biosynthesis of proTRH-derived peptides in prohormone convertase 1 and 2 knockout mice. Peptides. 2012;35:42-8 pubmed publisher
    ..Collectively, results characterize the specific roles of PC1 and PC2 in proTRH processing in vivo. ..
  49. Steiner D. On the discovery of precursor processing. Methods Mol Biol. 2011;768:3-11 pubmed publisher
    ..This brief report concentrates mainly on the role of insulin biosynthesis in providing a useful early paradigm of precursor processing in the secretory pathway. ..
  50. Winsky Sommerer R, Benjannet S, Rovere C, Barbero P, Seidah N, Epelbaum J, et al. Regional and cellular localization of the neuroendocrine prohormone convertases PC1 and PC2 in the rat central nervous system. J Comp Neurol. 2000;424:439-60 pubmed
  51. Meyer A, Chretien P, Massicotte G, Sargent C, Chretien M, Marcinkiewicz M. Kainic acid increases the expression of the prohormone convertases furin and PC1 in the mouse hippocampus. Brain Res. 1996;732:121-32 pubmed
    ..Based on colocalization studies and evidence of coordinate expression with NGF and BDNF, we suggest the involvement of furin in processing of proNGF, and of both furin and PC1 in processing of proBDNF. ..
  52. Hiramoto K, Yamate Y, Kobayashi H, Ishii M, Sato E, Inoue M. Ultraviolet B irradiation of the mouse eye induces pigmentation of the skin more strongly than does stress loading, by increasing the levels of prohormone convertase 2 and ?-melanocyte-stimulating hormone. Clin Exp Dermatol. 2013;38:71-6 pubmed publisher
    ..UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of ?-MSH and PC2. ..
  53. Shennan K, Taylor N, Docherty K. Calcium- and pH-dependent aggregation and membrane association of the precursor of the prohormone convertase PC2. J Biol Chem. 1994;269:18646-50 pubmed
  54. Holthuis J, Jansen E, Martens G. Secretogranin III is a sulfated protein undergoing proteolytic processing in the regulated secretory pathway. J Biol Chem. 1996;271:17755-60 pubmed
    ..We conclude that SgIII is a precursor protein and that the intact molecule can only have an intracellular function, whereas an extracellular role can only be attributed to its cleavage products. ..
  55. Damholt A, Buchan A, Holst J, Kofod H. Proglucagon processing profile in canine L cells expressing endogenous prohormone convertase 1/3 and prohormone convertase 2. Endocrinology. 1999;140:4800-8 pubmed
    ..This formation must then require an additional element to occur, or alternatively, the results could be explained by a canine specific organization of PC2 and Pg into separate compartments, which would prevent interaction. ..
  56. Wideman R, Covey S, Webb G, Drucker D, Kieffer T. A switch from prohormone convertase (PC)-2 to PC1/3 expression in transplanted alpha-cells is accompanied by differential processing of proglucagon and improved glucose homeostasis in mice. Diabetes. 2007;56:2744-52 pubmed
    ..This suggests that alteration of proglucagon processing in the alpha-cell may be therapeutically useful in the context of diabetes. ..
  57. Marzban L, Rhodes C, Steiner D, Haataja L, Halban P, Verchere C. Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death. Diabetes. 2006;55:2192-201 pubmed
  58. Fujita Y, Asadi A, Yang G, Kwok Y, Kieffer T. Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut. Am J Physiol Gastrointest Liver Physiol. 2010;298:G608-14 pubmed publisher
    ..Amidated GIP(1-30) and GIP(1-42) have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP(1-30) represents a naturally occurring, biologically active form of GIP. ..
  59. Yaoi Y, Suzuki M, Tomura H, Kurabuchi S, Sasayama Y, Tanaka S. Expression and localization of prohormone convertase PC1 in the calcitonin-producing cells of the bullfrog ultimobranchial gland. J Histochem Cytochem. 2003;51:1459-66 pubmed
    ..We conclude that the main prohormone convertase that is involved in the proteolytic cleavage of procalcitonin in the bullfrog is PC1...
  60. Helwig M, Lee S, Hwang J, Ozawa A, Medrano J, Lindberg I. Dynamic modulation of prohormone convertase 2 (PC2)-mediated precursor processing by 7B2 protein: preferential effect on glucagon synthesis. J Biol Chem. 2011;286:42504-13 pubmed publisher
    ..The manipulation of 7B2 could therefore represent an effective way to selectively regulate synthesis of certain PC2-dependent peptides. ..
  61. Wang J, Xu J, Finnerty J, Furuta M, Steiner D, Verchere C. The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. Diabetes. 2001;50:534-9 pubmed
    ..These data indicate that PC2 is essential for processing of proIAPP at the NH2-terminal cleavage site in vivo and that PC3 is likely only capable of processing proIAPP at the COOH-terminal cleavage site. ..
  62. Leak T, Keene K, Langefeld C, Gallagher C, Mychaleckyj J, Freedman B, et al. Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population. Mol Genet Metab. 2007;92:145-50 pubmed
    ..028), rs4814597 (Pa=0.039) and rs2269023 (Pa=0.043). None of the PCSK2 SNPs were associated with age at T2DM diagnosis. A variant in the PCKS2 gene, rs2021785, appears to play a role in susceptibility to T2DM in this AA population. ..
  63. Zhou A, Martin S, Lipkind G, LaMendola J, Steiner D. Regulatory roles of the P domain of the subtilisin-like prohormone convertases. J Biol Chem. 1998;273:11107-14 pubmed
    ..g. PC2/PC3Pd was inactive). The observed property changes indicate a role for the P domain in regulating the stability, calcium dependence, and pH dependence of the convertases. ..
  64. Börjesson A, Andersson A, Sandler S. Survival of an islet allograft deficient in iNOS after implantation into diabetic NOD mice. Cell Transplant. 2006;15:769-75 pubmed
  65. Toullec J, Kamech N, Gallois D, Maibeche M, Papon V, Boscameric M, et al. Molecular cloning and cellular expression of crustacean PC2-like prohormone convertase. Biochim Biophys Acta. 2002;1574:145-51 pubmed
    ..It was demonstrated by in situ hybridization on crayfish medulla terminalis sections that OrlPC2 is expressed in a large number of neuron perikarya, including those producing the well known crustacean hyperglycemic hormone. ..
  66. Galanopoulou A, Seidah N, Patel Y. Heterologous processing of rat prosomatostatin to somatostatin-14 by PC2: requirement for secretory cell but not the secretion granule. Biochem J. 1995;311 ( Pt 1):111-8 pubmed
    ..The activity of PC2 requires the milieu of the secretory cell but not the secretory granule. ..
  67. Peinado J, Laurent V, Lee S, Peng B, Pintar J, Steiner D, et al. Strain-dependent influences on the hypothalamo-pituitary-adrenal axis profoundly affect the 7B2 and PC2 null phenotypes. Endocrinology. 2005;146:3438-44 pubmed
  68. Winsky Sommerer R, Grouselle D, Rougeot C, Laurent V, David J, Delacourte A, et al. The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease. Neuroscience. 2003;122:437-47 pubmed
    ..Therefore, the cortical somatostatin defect is not due to convertase alteration occuring during Alzheimer's disease. Further studies will be needed to assess the mechanisms involved in somatostatin deficiency in Alzheimer's disease. ..
  69. Rehfeld J, Lindberg I, Friis Hansen L. Increased synthesis but decreased processing of neuronal proCCK in prohormone convertase 2 and 7B2 knockout animals. J Neurochem. 2002;83:1329-37 pubmed
    ..The results show that PC2 plays a major neuron-specific role in the processing of proCCK. ..
  70. Shibru D, Hwang J, Khanafshar E, Duh Q, Clark O, Kebebew E. Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?. Cancer. 2008;113:930-5 pubmed publisher
  71. Guillemot J, Thouennon E, Guerin M, Vallet Erdtmann V, Ravni A, Montero Hadjadje M, et al. Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66. J Mol Endocrinol. 2012;48:115-27 pubmed publisher
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