Gene Symbol: Pcsk2
Description: proprotein convertase subtilisin/kexin type 2
Alias: 6330411F23Rik, AI839700, Nec-2, Nec2, PC2, Phpp-2, SPC2, neuroendocrine convertase 2, KEX2-like endoprotease 2, NEC 2, prohormone convertase 2, proprotein convertase 2
Species: mouse
Products:     Pcsk2

Top Publications

  1. Laurent V, Jaubert Miazza L, Desjardins R, Day R, Lindberg I. Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice. Endocrinology. 2004;145:519-28 pubmed
    ..The maturation of PC2 requires the aid of a helper protein, 7B2, in order for the zymogen to become an active enzyme species...
  2. St Germain C, Croissandeau G, Mayne J, Baltz J, Chretien M, Mbikay M. Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development. Mol Reprod Dev. 2005;72:483-93 pubmed
    ..Transcripts for all PCs, except PC2, were detected by reverse transcription-polymerase chain reaction (RT-PCR) in unfertilized and fertilized eggs...
  3. Steiner D, Smeekens S, Ohagi S, Chan S. The new enzymology of precursor processing endoproteases. J Biol Chem. 1992;267:23435-8 pubmed
  4. Constam D, Robertson E. Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases. J Cell Biol. 1999;144:139-49 pubmed
    ..Collectively, these data show that the half-life of mature BMPs is greatly influenced by the identity of their pro regions. ..
  5. Furuta M, Carroll R, Martin S, Swift H, Ravazzola M, Orci L, et al. Incomplete processing of proinsulin to insulin accompanied by elevation of Des-31,32 proinsulin intermediates in islets of mice lacking active PC2. J Biol Chem. 1998;273:3431-7 pubmed
    The prohormone convertases PC2 (SPC2) and PC3/PC1 (SPC3) are the major precursor processing endoproteases in a wide variety of neural and endocrine tissues...
  6. 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
    The prohormone convertase SPC2 (PC2) participates in the processing of proinsulin, proglucagon, and a variety of other neuroendocrine precursors, acting either alone or in conjunction with the structurally related dense-core granule ..
  7. Talchai C, Xuan S, Kitamura T, Depinho R, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet. 2012;44:406-12, S1 pubmed publisher
    ..The data indicate that Neurog3(+) enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins(+) cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes. ..
  8. Gagnon J, Mayne J, Chen A, Raymond A, Woulfe J, Mbikay M, et al. PCSK2-null mice exhibit delayed intestinal motility, reduced refeeding response and altered plasma levels of several regulatory peptides. Life Sci. 2011;88:212-7 pubmed publisher
    To examine the effects of global lack of proprotein convertase subtilisin/kexin 2 (PCSK2) in mouse on intestinal motility, post-fast refeeding response and levels of several PCSK-generated peptides known to regulate food intake and ..
  9. Tang S, Zhang J, Liu H, Li H. PC2/CPE-mediated pro-protein processing in tumor cells and its differentiated cells or tissues. Mol Cell Endocrinol. 2009;303:43-9 pubmed publisher
    Pro-protein convertase-2 (PC2) and carboxypeptidase-E (CPE) proteins are two major members of the pro-protein convertases that involve in the maturation of protein precursor...

More Information


  1. Laslop A, Becker A, Lindberg I, Fischer Colbrie R. Proteolytic processing of chromogranins is modified in brains of transgenic mice. Ann N Y Acad Sci. 2002;971:49-52 pubmed
    ..After genetic knockout of PC2 or its helper protein 7B2, but not after mutation of carboxypeptidase E, endoproteolytic processing decreased, as ..
  2. Rehfeld J, Zhu X, Norrbom C, Bundgaard J, Johnsen A, Nielsen J, et al. Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17. Biochem J. 2008;415:35-43 pubmed publisher
    ..alpha-amidated gastrins in antral extracts from PC1/3-null mice and compared the results with those in mice lacking PC2 and wild-type controls...
  3. Benjannet S, Lusson J, Hamelin J, Savaria D, Chretien M, Seidah N. Structure-function studies on the biosynthesis and bioactivity of the precursor convertase PC2 and the formation of the PC2/7B2 complex. FEBS Lett. 1995;362:151-5 pubmed
    Site directed mutagenesis of the prohormone convertase PC2 was used to define the effect of certain residues on the zymogen activation of proPC2 and on its binding to the neuroendocrine protein 7B2...
  4. 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. ..
  5. Lee S, Lindberg I. 7B2 prevents unfolding and aggregation of prohormone convertase 2. Endocrinology. 2008;149:4116-27 pubmed publisher
    b>Prohormone convertase 2 (PC2) requires interaction with the neuroendocrine protein 7B2 for the production of an activatable zymogen; the mechanism for this effect is unknown...
  6. Zhang X, Pan H, Peng B, Steiner D, Pintar J, Fricker L. Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis. J Neurochem. 2010;112:1168-79 pubmed publisher
    b>Prohormone convertase 2 (PC2) functions in the generation of neuropeptides from their precursors. A quantitative peptidomics approach was used to evaluate the role of PC2 in the processing of peptides in a variety of brain regions...
  7. Chen Y, Cao W, Zhou S, Shen L, Wen J. Mutant PAX6 downregulates prohormone convertase 2 expression in mouse islets. Exp Biol Med (Maywood). 2013;238:1259-64 pubmed publisher
    ..b>Prohormone convertase 2 (PC2) is the essential enzyme for pancreatic proinsulin processing...
  8. Courtade J, Wang E, Yen P, Dai D, Soukhatcheva G, Orban P, et al. Loss of prohormone convertase 2 promotes beta cell dysfunction in a rodent transplant model expressing human pro-islet amyloid polypeptide. Diabetologia. 2017;60:453-463 pubmed publisher
    ..IAPP is derived from a prohormone precursor, proIAPP, which requires cleavage by prohormone convertase (PC) 1/3 and PC2 in rodent pancreatic beta cells...
  9. Mbikay M, Raffin Sanson M, Sirois F, Kalenga L, Chretien M, Seidah N. Characterization of a repressor element in the promoter region of proprotein convertase 2 (PC2) gene. Brain Res Mol Brain Res. 2002;102:35-47 pubmed
    The proprotein convertase PC2 is primarily expressed in neuroendocrine cells where it mediates the proteolytic maturation of prohormones and proneuropeptides...
  10. Seidah N, Mattei M, Gaspar L, Benjannet S, Mbikay M, Chretien M. Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region). Genomics. 1991;11:103-7 pubmed
    The chromosomal localization of the genes coding for the pro-protein and pro-hormone convertases PC1, PC2, and Furin has been achieved by in situ hybridization...
  11. Ugleholdt R, Poulsen M, Holst P, Irminger J, Orskov C, Pedersen J, et al. Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. J Biol Chem. 2006;281:11050-7 pubmed
    ..This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression...
  12. Refaie S, Gagnon S, Gagnon H, Desjardins R, D Anjou F, D Orléans Juste P, et al. Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion. J Biol Chem. 2012;287:14703-17 pubmed publisher
    ..PC1/3 KO mice are more susceptible to septic shock than wild-type controls or other PC KO mice, such as PC2 and PC7 null mice...
  13. Decroly E, Wouters S, Di Bello C, Lazure C, Ruysschaert J, Seidah N. Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines. J Biol Chem. 1996;271:30442-50 pubmed
    ..The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the major gp160-converting enzymes in T4 lymphocytes. ..
  14. 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
    The serine protease prohormone convertase 2 (PC2), principally involved in the processing of polypeptide hormone precursors in neuroendocrine tissues, requires interaction with the neuroendocrine protein 7B2 to generate an enzymatically ..
  15. Hardiman A, Friedman T, Grunwald W, Furuta M, Zhu Z, Steiner D, et al. Endocrinomic profile of neurointermediate lobe pituitary prohormone processing in PC1/3- and PC2-Null mice using SELDI-TOF mass spectrometry. J Mol Endocrinol. 2005;34:739-51 pubmed
    ..Neurointermediate lobe pituitaries from normal (+/+), heterozygous (+/-), PC2-Null (-/-), PC1/3-Null and oxytocin-Null mice were analyzed by SELDI-TOF mass spectroscopy for the peptide hormone ..
  16. 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
    ..To gain insight into the role of prohormone convertases PC1, PC2, and PC7 in this process, we investigated the maturation of pro-NT/NN in the brain of PC7 (PC7-/-), PC2 (PC2-/-), ..
  17. 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 small neuroendocrine protein 7B2 is required for the production of active prohormone convertase 2 (PC2), an enzyme involved in the synthesis of peptide hormones, such as glucagon and proopiomelanocortin-derived ?-melanocyte-..
  18. Warden C, Stone S, Chiu S, Diament A, Corva P, Shattuck D, et al. Identification of a congenic mouse line with obesity and body length phenotypes. Mamm Genome. 2004;15:460-71 pubmed
    ..Since a previous study identified human obesity linkage peaking near the centromere, then the B10.UW mice may exhibit obesity due to the homologous gene...
  19. Rehfeld J, Bungaard J, Friis Hansen L, Goetze J. On the tissue-specific processing of procholecystokinin in the brain and gut--a short review. J Physiol Pharmacol. 2003;54 Suppl 4:73-9 pubmed
    ..Of these, PC1 and PC2 are expressed in cerebral neurons and intestinal endocrine cells...
  20. 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
    We present herein the pulse-chase analysis of the biosynthesis of the prohormone convertases PC1 and PC2 in the endocrine GH4C1 cells infected with vaccinia virus recombinants expressing these convertases...
  21. Lee S, Kacprzak M, Day R, Lindberg I. Processing and trafficking of a prohormone convertase 2 active site mutant. Biochem Biophys Res Commun. 2007;355:825-9 pubmed
    ..We here report that the active site serine mutant of PC2 (PC2-S383A) was efficiently secreted as the intact zymogen in CHO-K1 cells, suggesting that its propeptide can ..
  22. Lee C, Sund N, Behr R, Herrera P, Kaestner K. Foxa2 is required for the differentiation of pancreatic alpha-cells. Dev Biol. 2005;278:484-95 pubmed
    ..By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation. ..
  23. Dames P, Puff R, Weise M, Parhofer K, Goke B, Gotz M, et al. Relative roles of the different Pax6 domains for pancreatic alpha cell development. BMC Dev Biol. 2010;10:39 pubmed publisher
    ..This function is differentially affected by the two homeodomain mutations analyzed in this study. ..
  24. Miller R, Toneff T, Vishnuvardhan D, Beinfeld M, Hook V. Selective roles for the PC2 processing enzyme in the regulation of peptide neurotransmitter levels in brain and peripheral neuroendocrine tissues of PC2 deficient mice. Neuropeptides. 2003;37:140-8 pubmed
    The prohormone convertase 2 (PC2) is hypothesized to convert multiple pro-neuropeptides into active peptides that function as neurotransmitters...
  25. Vishnuvardhan D, Connolly K, Cain B, Beinfeld M. PC2 and 7B2 null mice demonstrate that PC2 is essential for normal pro-CCK processing. Biochem Biophys Res Commun. 2000;273:188-91 pubmed
    Analysis of CCK content in extracts of whole forebrain from PC2 and 7B2 null mouse brain showed a significant decrease relative to wild-type brains...
  26. Rehfeld J, Lindberg I, Friis Hansen L. Progastrin processing differs in 7B2 and PC2 knockout animals: a role for 7B2 independent of action on PC2. FEBS Lett. 2002;510:89-93 pubmed
    ..In order to determine the role of PC2 for gastrin synthesis, we examined antral extracts from mice lacking PC2 or its chaperone, 7B2...
  27. Furuta M, Zhou A, Webb G, Carroll R, Ravazzola M, Orci L, et al. Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice. J Biol Chem. 2001;276:27197-202 pubmed
    Mice homozygous for a deletion in the gene encoding prohormone convertase 2 (PC2) are generally healthy but have mild hypoglycemia and flat glucose-tolerance curves...
  28. 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
    ..The prohormone convertase enzymes PC3 (also known as PC1) and PC2 are localized to beta-cell secretory granules with proIAPP and proinsulin and are responsible for proinsulin ..
  29. Lutfy K, Parikh D, Lee D, Liu Y, Ferrini M, Hamid A, et al. Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence. Neuroscience. 2016;329:318-25 pubmed publisher
    Chronic morphine treatment increases the levels of prohormone convertase 2 (PC2) in brain regions involved in nociception, tolerance and dependence...
  30. Seidah N, Marcinkiewicz M, Benjannet S, Gaspar L, Beaubien G, Mattei M, et al. Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2. Mol Endocrinol. 1991;5:111-22 pubmed
    ..47% amino acid sequence identity to the recently characterized candidate prohormone convertases human Furin, mouse PC2, and yeast Kex2 gene products, respectively...
  31. Poirier S, Prat A, Marcinkiewicz E, Paquin J, Chitramuthu B, Baranowski D, et al. Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system. J Neurochem. 2006;98:838-50 pubmed
    ..convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4 days of the differentiation period respectively...
  32. Pan H, Che F, Peng B, Steiner D, Pintar J, Fricker L. The role of prohormone convertase-2 in hypothalamic neuropeptide processing: a quantitative neuropeptidomic study. J Neurochem. 2006;98:1763-77 pubmed
    ..A quantitative peptidomic approach was used to explore the role PC2 plays in the processing of hypothalamic peptides...
  33. Croissandeau G, Wahnon F, Yashpal K, Seidah N, Coderre T, Chretien M, et al. Increased stress-induced analgesia in mice lacking the proneuropeptide convertase PC2. Neurosci Lett. 2006;406:71-5 pubmed
    ..are generated by endoproteolytic cleavages of their precursor proteins by the proprotein convertases PC1 and PC2. To investigate the role of PC2 in nociception and analgesia, we tested wild-type and PC2-null mice for their ..
  34. Raetzman L, Cai J, Camper S. Hes1 is required for pituitary growth and melanotrope specification. Dev Biol. 2007;304:455-66 pubmed
    ..These results demonstrate that Notch signaling plays multiple roles in pituitary development, influencing precursor number, organ size, cell differentiation and ultimately cell fate. ..
  35. 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
    ..We compared the effect of transplanting encapsulated PC2-expressing alpha TC-1 cells with PC1/3-expressing alpha TCDeltaPC2 cells in normal mice and low-dose streptozotocin ..
  36. Mesnard D, Constam D. Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst. J Cell Biol. 2010;191:129-39 pubmed publisher
    ..The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo. ..
  37. Marcinkiewicz M, Ramla D, Seidah N, Chretien M. Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets. Endocrinology. 1994;135:1651-60 pubmed
    The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets...
  38. Grigoryan M, Kedees M, Guz Y, Teitelman G. Phenotype of entero-endocrine L cells becomes restricted during development. Dev Dyn. 2012;241:1986-92 pubmed publisher
    ..Glu-positive cells contain proprotein-convertase 2 (PC2) and PC3/1, the enzymes responsible for Glu and GLP-1 synthesis, respectively...
  39. Nakamoto K, Aizawa F, Nishinaka T, Tokuyama S. Regulation of prohormone convertase 2 protein expression via GPR40/FFA1 in the hypothalamus. Eur J Pharmacol. 2015;762:459-63 pubmed publisher
    ..The intracerebroventricular injection of DHA or GW9508 significantly increased PC2 protein expression in the hypothalamus...
  40. Wang C, Brodnicki T, Copeland N, Jenkins N, Harvey R. Conserved linkage of NK-2 homeobox gene pairs Nkx2-2/2-4 and Nkx2-1/2-9 in mammals. Mamm Genome. 2000;11:466-8 pubmed
  41. 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
    Two null mouse models have previously been created to study the role of the prohormone convertase (PC2) and its helper protein 7B2; unexpectedly, the phenotypes of these two nulls differ profoundly, with the 7B2 but not the PC2 null ..
  42. Marzban L, Trigo Gonzalez G, Zhu X, Rhodes C, Halban P, Steiner D, et al. Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide. Diabetes. 2004;53:141-8 pubmed
    ..the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2. Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 ..
  43. MacLaren E, Bennett B, Johnson T, Sikela J. Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs. Mamm Genome. 2006;17:147-56 pubmed
    ..These genes represent novel candidates for the LORR phenotype and provide new targets for future studies into the neuronal processes underlying ethanol sensitivity. ..
  44. Pataskar A, Jung J, Smialowski P, Noack F, Calegari F, Straub T, et al. NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program. EMBO J. 2016;35:24-45 pubmed publisher
  45. Wilson M, Kalamaras J, German M. Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas. Mech Dev. 2002;115:171-6 pubmed
    ..The early production of atypical peptide hormones by these cells suggests that they could play an important role locally or systemically in the development of the embryo. ..
  46. Hess E, Collins K, Copeland N, Jenkins N, Wilson M. Deletion map of the coloboma (Cm) locus on mouse chromosome 2. Genomics. 1994;21:257-61 pubmed
    ..1 to 2.2 cM that may be probed for genes, both in the mouse and in the syntenic region of human Chr 20, that independently affect elements of neurological behavior and eye development. ..
  47. 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
    ..3-kDa fragment, and free Leu5-enkephalin. PC2 exhibited a more complete processing profile...
  48. Wardman J, Zhang X, Gagnon S, Castro L, Zhu X, Steiner D, et al. Analysis of peptides in prohormone convertase 1/3 null mouse brain using quantitative peptidomics. J Neurochem. 2010;114:215-25 pubmed publisher
    ..Major endopeptidases required for these cleavages include prohormone convertase (PC) 1/3 and PC2. In this study, quantitative peptidomics analysis was used to characterize the specific role PC1/3 plays in this ..
  49. Seidah N, Chretien M. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res. 1999;848:45-62 pubmed
    ..Seven mammalian precursor convertases (PCs) have been identified: PC1, PC2, furin, PC4, PC5, PACE4 and PC7...
  50. Marcinkiewicz M, Day R, Seidah N, Chretien M. Ontogeny of the prohormone convertases PC1 and PC2 in the mouse hypophysis and their colocalization with corticotropin and alpha-melanotropin. Proc Natl Acad Sci U S A. 1993;90:4922-6 pubmed
    ..POMC products are likely the result of differential expression of the two known prohormone convertases PC1 and PC2. In the present ontogeny study done in the mouse intermediate and anterior pituitary, we examined how the ..
  51. 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
    ..Comparative studies of PC1/3 and PC2 convertases showed that PC1/3 knockout mouse brains had a modest decrease in dynorphin A, and PC2 knockout mice ..
  52. Lock L, Wickramasinghe D, Ernst M, Gilbert D, Copeland N, Jenkins N, et al. The Cdc25 genes map to mouse chromosomes 2, 9, and 18. Mamm Genome. 1996;7:771-2 pubmed
  53. Schaner P, Todd R, Seidah N, Nillni E. Processing of prothyrotropin-releasing hormone by the family of prohormone convertases. J Biol Chem. 1997;272:19958-68 pubmed
    ..We have also demonstrated that recombinant PC1 and PC2 process partially purified pro-TRH to cryptic peptides in vitro and that pro-TRH and PC1 mRNAs are coexpressed in ..
  54. Dikeakos J, Mercure C, Lacombe M, Seidah N, Reudelhuber T. PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism. FEBS J. 2007;274:4094-102 pubmed
    ..PC1/3, PC2 and PC5/6A are the only members of the PC family that are targeted to dense core secretory granules, where they ..
  55. Kedees M, Guz Y, Vuguin P, Vargas C, Cui L, Steiner D, et al. Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling. Dev Dyn. 2007;236:1126-33 pubmed
    ..One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2(-/-)), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a ..
  56. 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
    The neuroendocrine protein 7B2 has been implicated in activation of prohormone convertase 2 (PC2), an important neuroendocrine precursor processing endoprotease...
  57. Kayo T, Fujita H, Nozaki J, E X, Koizumi A. Identification of two chromosomal loci determining glucose intolerance in a C57BL/6 mouse strain. Comp Med. 2000;50:296-302 pubmed
    ..2 in F3. Direct sequencing of candidate genes, proprotein convertase-2 (PC2) on chromosome 2 and proprotein convertase-1/3 (PC1/PC3) on chromosome 13, failed to reveal a mutation or ..
  58. Zhu X, Cao Y, Voogd K, Voodg K, Steiner D. On the processing of proghrelin to ghrelin. J Biol Chem. 2006;281:38867-70 pubmed
  59. Berman Y, Mzhavia N, Polonskaia A, Furuta M, Steiner D, Pintar J, et al. Defective prodynorphin processing in mice lacking prohormone convertase PC2. J Neurochem. 2000;75:1763-70 pubmed
    ..Among the prohormone convertases (PCs), PC1 and PC2 are expressed widely in neuroendocrine tissues and have been proposed to be the major convertases involved in the ..
  60. Jones H, Reens J, Brocklehurst S, Betts C, Bickerton S, Bigley A, et al. Islets of Langerhans from prohormone convertase-2 knockout mice show ?-cell hyperplasia and tumorigenesis with elevated ?-cell neogenesis. Int J Exp Pathol. 2014;95:29-48 pubmed publisher
    ..the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice (PC2-ko), in which ?-cell hyperplasia is present from a young age and persists throughout life, in order to understand ..
  61. Seidah N, Chretien M, Day R. The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions. Biochimie. 1994;76:197-209 pubmed
    ..These subtilisin/kexin-like convertases were called furin/PACE, PC1/PC3, PC2, PACE4, PC4 and PC5/PC6...
  62. 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
    ..STC-1 cells, a mouse intestinal tumor cell line that expresses CCK, PC1, PC2, and PC5 were stably transfected with hairpin loop plasmids encoding siRNA targeting PC5 and clones were selected...
  63. 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
    ..Previous evidence suggests that PC1 is responsible for most proTRH cleavage events. Here, we used the PC1 and PC2 knockout (KO) mouse models to examine the effects of PC1 or PC2 loss on proTRH processing...
  64. Dey A, Xhu X, Carroll R, Turck C, Stein J, Steiner D. Biological processing of the cocaine and amphetamine-regulated transcript precursors by prohormone convertases, PC2 and PC1/3. J Biol Chem. 2003;278:15007-14 pubmed
    ..have shown that pro-CART is a substrate for the neuroendocrine subtilisin/kexin-like prohormone convertases, PC2 (SPC2) and PC1/3 (SPC3)...
  65. Kita A, Imayoshi I, Hojo M, Kitagawa M, Kokubu H, Ohsawa R, et al. Hes1 and Hes5 control the progenitor pool, intermediate lobe specification, and posterior lobe formation in the pituitary development. Mol Endocrinol. 2007;21:1458-66 pubmed
    ..Thus, Hes genes control not only maintenance of progenitor cells but also intermediate vs. anterior lobe specification during the adenohypophysis development. Hes genes are also essential for the formation of the neurohypophysis. ..
  66. Himes A, Raetzman L. Premature differentiation and aberrant movement of pituitary cells lacking both Hes1 and Prop1. Dev Biol. 2009;325:151-61 pubmed publisher
    ..Our data reveal important overlapping functions of Hes1 and Prop1 in cell differentiation and movement that are critical for pituitary organogenesis. ..
  67. Chiu S, Kim K, Haus K, Espinal G, Millon L, Warden C. Identification of positional candidate genes for body weight and adiposity in subcongenic mice. Physiol Genomics. 2007;31:75-85 pubmed
    ..S-2A subcongenic donor region, including prohormone convertase 2 (PC2; gene name: Pcsk2)...
  68. 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
    b>Prohormone convertase 2 (PC2) plays an essential role in the processing of proglucagon to mature active glucagon in pancreatic alpha-cells (J Biol Chem 276:27197-27202, 2001)...
  69. Yu R. Animal models of spontaneous pancreatic neuroendocrine tumors. Mol Cell Endocrinol. 2016;421:60-7 pubmed publisher
    ..Future studies on animal models of PNETs should address early tumor detection, molecular markers of tumor behavior, and novel targeted therapies. ..
  70. Webb G, Dey A, Wang J, Stein J, Milewski M, Steiner D. Altered proglucagon processing in an alpha-cell line derived from prohormone convertase 2 null mouse islets. J Biol Chem. 2004;279:31068-75 pubmed
    ..The main PC family members expressed in mammalian neuroendocrine cells are PC2 and PC1/3...
  71. Miller R, Aaron W, Toneff T, Vishnuvardhan D, Beinfeld M, Hook V. Obliteration of alpha-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice. J Neurochem. 2003;86:556-63 pubmed
    ..Therefore, this study investigated the in vivo role of the prohormone convertase 2 (PC2) processing enzyme for production of alpha-MSH in PC2-deficient mice...
  72. Sander M, Sussel L, Conners J, Scheel D, Kalamaras J, Dela Cruz F, et al. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development. 2000;127:5533-40 pubmed
    ..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation. ..
  73. Diament A, Farahani P, Chiu S, Fisler J, Warden C. A novel mouse Chromosome 2 congenic strain with obesity phenotypes. Mamm Genome. 2004;15:452-9 pubmed
    ..The obesity phenotype of the QTL is retained in the congenic. The congenic can now be used to model the genetic and physiological basis for a relatively simple, perhaps monogenic, obesity...