carboxypeptidase h

Summary

Summary: A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.

Top Publications

  1. Naggert J, Fricker L, Varlamov O, Nishina P, Rouille Y, Steiner D, et al. Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat Genet. 1995;10:135-42 pubmed
    ..Thus, the fat mutation represents the first demonstration of an obesity-diabetes syndrome elicited by a genetic defect in a prohormone processing pathway. ..
  2. Qian Y, Varlamov O, Fricker L. Glu300 of rat carboxypeptidase E is essential for enzymatic activity but not substrate binding or routing to the regulated secretory pathway. J Biol Chem. 1999;274:11582-6 pubmed
    ..Taken together, these results indicate that Glu300 of CPE is essential for enzyme activity, but not required for substrate binding or for routing into the regulated secretory pathway. ..
  3. Cawley N, Wetsel W, Murthy S, Park J, Pacak K, Loh Y. New roles of carboxypeptidase E in endocrine and neural function and cancer. Endocr Rev. 2012;33:216-53 pubmed publisher
    Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin...
  4. Fan X, Olson S, Blevins L, Allen G, Johnson M. Immunohistochemical localization of carboxypeptidases D, E, and Z in pituitary adenomas and normal human pituitary. J Histochem Cytochem. 2002;50:1509-16 pubmed
    ..CPE in these cells may process other peptides critical for pituitary cell function, such as chromogranin A or B. These findings suggest that CPs participate in the functioning of pituitary adenomas. ..
  5. Johnston R, Theman T, Shore S. Augmented responses to ozone in obese carboxypeptidase E-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2006;290:R126-33 pubmed
    ..These results also suggest that chronic systemic inflammation may enhance airway responses to O3 in obese mice. ..
  6. Jin K, Graham S, Nagayama T, Goldsmith P, Greenberg D, Zhou A, et al. Altered expression of the neuropeptide-processing enzyme carboxypeptidase E in the rat brain after global ischemia. J Cereb Blood Flow Metab. 2001;21:1422-9 pubmed
    ..The ischemia-induced changes in carboxypeptidase E expression suggest that this enzyme may play a role in modulating the brain's response to ischemia. ..
  7. Lou H, Kim S, Zaitsev E, Snell C, Lu B, Loh Y. Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase e. Neuron. 2005;45:245-55 pubmed
    ..Thus, we have identified a mechanism whereby a specific motif I(16)E(18)I(105)D(106) interacts with CPE to sort proBDNF into regulated pathway vesicles for activity-dependent secretion. ..
  8. Zhou A, Minami M, Zhu X, Bae S, Minthorne J, Lan J, et al. Altered biosynthesis of neuropeptide processing enzyme carboxypeptidase E after brain ischemia: molecular mechanism and implication. J Cereb Blood Flow Metab. 2004;24:612-22 pubmed
    ..These findings suggest that ischemia has an adverse impact on the neuropeptide-processing system in the brain and that the lack of an active neuropeptide-processing enzyme exacerbates ischemic brain injury. ..
  9. Shen F, Loh Y. Intracellular misrouting and abnormal secretion of adrenocorticotropin and growth hormone in cpefat mice associated with a carboxypeptidase E mutation. Proc Natl Acad Sci U S A. 1997;94:5314-9 pubmed

More Information

Publications88

  1. Höring E, Harter P, Seznec J, Schittenhelm J, Buhring H, Bhattacharyya S, et al. The "go or grow" potential of gliomas is linked to the neuropeptide processing enzyme carboxypeptidase E and mediated by metabolic stress. Acta Neuropathol. 2012;124:83-97 pubmed publisher
  2. Woronowicz A, Koshimizu H, Chang S, Cawley N, Hill J, Rodriguiz R, et al. Absence of carboxypeptidase E leads to adult hippocampal neuronal degeneration and memory deficits. Hippocampus. 2008;18:1051-63 pubmed publisher
    ..These findings taken together indicate that CPE is essential for the survival of adult hippocampal CA3 neurons to maintain normal cognitive function. ..
  3. Cawley N, Yanik T, Woronowicz A, Chang W, Marini J, Loh Y. Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density. Am J Physiol Endocrinol Metab. 2010;299:E189-97 pubmed publisher
  4. Dhanvantari S, Arnaoutova I, Snell C, Steinbach P, Hammond K, Caputo G, et al. Carboxypeptidase E, a prohormone sorting receptor, is anchored to secretory granules via a C-terminal transmembrane insertion. Biochemistry. 2002;41:52-60 pubmed
  5. Chen H, Jawahar S, Qian Y, Duong Q, Chan G, Parker A, et al. Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity. Hum Mutat. 2001;18:120-31 pubmed
    ..We predict that this mutant could cause hyperproinsulinism and diabetes in the homozygous state. ..
  6. 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
  7. Utsunomiya N, Ohagi S, Sanke T, Tatsuta H, Hanabusa T, Nanjo K. Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity. Diabetologia. 1998;41:701-5 pubmed
    ..None of the nucleotide substitutions were associated with NIDDM or obesity. Thus, genetic variation in the CPE gene does not appear to play a major role in the pathogenesis of NIDDM or obesity in Japanese subjects. ..
  8. Jackson R, Creemers J, Ohagi S, Raffin Sanson M, Sanders L, Montague C, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet. 1997;16:303-6 pubmed
    ..In view of the similarity between the proband and the fat/fat mouse phenotype, we infer that molecular defects in prohormone conversion may represent a generic mechanism for obesity, common to humans and rodents. ..
  9. Cool D, Normant E, Shen F, Chen H, Pannell L, Zhang Y, et al. Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. Cell. 1997;88:73-83 pubmed
    ..Thus, obliteration of CPE, the sorting receptor, leads to multiple endocrine disorders in these genetically defective mice, including hyperproinsulinemia and infertility. ..
  10. He P, Varticovski L, Bowman E, Fukuoka J, Welsh J, Miura K, et al. Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Hum Pathol. 2004;35:1196-209 pubmed
    ..Thus, cDNA microarray analysis led to the identification of 2 novel biomarkers that should facilitate molecular diagnosis and further study of pulmonary neuroendocrine tumors. ..
  11. Guest P, Arden S, Rutherford N, Hutton J. The post-translational processing and intracellular sorting of carboxypeptidase H in the islets of Langerhans. Mol Cell Endocrinol. 1995;113:99-108 pubmed
    The post-translational processing and intracellular sorting of the proinsulin-converting enzyme carboxypeptidase H (CPH) was studied in isolated rat islets of Langerhans...
  12. Murthy S, Pacak K, Loh Y. Carboxypeptidase E: elevated expression correlated with tumor growth and metastasis in pheochromocytomas and other cancers. Cell Mol Neurobiol. 2010;30:1377-81 pubmed publisher
    ..Thus, collectively the data suggest that CPE may play a role in promoting tumor growth and invasion. CPE could potentially serve as a diagnostic and prognostic biomarker for metastasis in different cancer types. ..
  13. Jeffrey K, Alejandro E, Luciani D, Kalynyak T, Hu X, Li H, et al. Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis. Proc Natl Acad Sci U S A. 2008;105:8452-7 pubmed publisher
    ..Thus, carboxypeptidase E degradation contributes to palmitate-induced beta-cell ER stress and apoptosis. CPE is a major link between hyperlipidemia and beta-cell death pathways in diabetes. ..
  14. Lou H, Park J, Cawley N, Sarcon A, Sun L, Adams T, et al. Carboxypeptidase E cytoplasmic tail mediates localization of synaptic vesicles to the pre-active zone in hypothalamic pre-synaptic terminals. J Neurochem. 2010;114:886-96 pubmed publisher
    ..Our findings identify the CPE cytoplasmic tail, as a new mediator for the localization of SVs in the actin-rich pre-active zone in hypothalamic neurons and the TIRF zone of PC12 cells. ..
  15. Fricker L, Snyder S. Enkephalin convertase: purification and characterization of a specific enkephalin-synthesizing carboxypeptidase localized to adrenal chromaffin granules. Proc Natl Acad Sci U S A. 1982;79:3886-90 pubmed
    ..Enkephalin convertase appears to be associated selectively and physiologically with biosynthesis of the enkephalins. ..
  16. Che F, Yan L, Li H, Mzhavia N, Devi L, Fricker L. Identification of peptides from brain and pituitary of Cpe(fat)/Cpe(fat) mice. Proc Natl Acad Sci U S A. 2001;98:9971-6 pubmed
    ..In addition, the general technique of using affinity chromatography to isolate endogenous substrates from a mutant organism lacking an enzyme should be applicable to a wide range of enzyme-substrate systems. ..
  17. Fan X, Olson S, Johnson M. Immunohistochemical localization and comparison of carboxypeptidases D, E, and Z, alpha-MSH, ACTH, and MIB-1 between human anterior and corticotroph cell "basophil invasion" of the posterior pituitary. J Histochem Cytochem. 2001;49:783-90 pubmed
    ..Evidence that corticotrophs in basophil invasion are undergoing proliferation and are also phenotypically different from their counterpart in the anterior pituitary has further raised the possibility of some neoplastic potential. ..
  18. Cawley N, Zhou J, Hill J, Abebe D, Romboz S, Yanik T, et al. The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits. Endocrinology. 2004;145:5807-19 pubmed
  19. Lee T, Murthy S, Cawley N, Dhanvantari S, Hewitt S, Lou H, et al. An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers. J Clin Invest. 2011;121:880-92 pubmed publisher
    ..Thus, CPE-?N induces tumor metastasis and should be investigated as a potentially powerful biomarker for predicting future metastasis and recurrence in HCC and PHEO/PGL patients. ..
  20. Plá V, Paco S, Ghezali G, Ciria V, Pozas E, Ferrer I, et al. Secretory sorting receptors carboxypeptidase E and secretogranin III in amyloid ?-associated neural degeneration in Alzheimer's disease. Brain Pathol. 2013;23:274-84 pubmed publisher
    ..Because CPE and SgIII are essential in the process and targeting of neuropeptides and neurotrophins, their participation in the pathological progression of AD may be suggested. ..
  21. Park J, Cawley N, Loh Y. A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons. Mol Cell Neurosci. 2008;39:63-73 pubmed publisher
    ..Thus, the CPE cytoplasmic tail binds dynactin that recruits kinesins or dynein for driving bi-directional transport of BDNF vesicle to maintain vesicle homeostasis and secretion in hippocampal neurons. ..
  22. Krajnik M, Schafer M, Sobanski P, Kowalewski J, Bloch Boguslawska E, Zylicz Z, et al. Enkephalin, its precursor, processing enzymes, and receptor as part of a local opioid network throughout the respiratory system of lung cancer patients. Hum Pathol. 2010;41:632-42 pubmed publisher
    ..These findings encourage future studies to examine the functional role of local opioid peptides within the respiratory system...
  23. Parkinson D. Two soluble forms of bovine carboxypeptidase H have different NH2-terminal sequences. J Biol Chem. 1990;265:17101-5 pubmed
    b>Carboxypeptidase H is an important enzyme in the biosynthesis of many peptide hormones. Development of a rapid isolation procedure led to the purification of two soluble forms from acidic extracts of bovine pituitary glands...
  24. Guest P, Abdel Halim S, Gross D, Clark A, Poitout V, Amaria R, et al. Proinsulin processing in the diabetic Goto-Kakizaki rat. J Endocrinol. 2002;175:637-47 pubmed
    ..Thus, the marked changes in islet morphology and PC2 expression did not impact the rate or extent of proinsulin processing either in vitro or in vivo in this experimental model. ..
  25. Aloy P, Companys V, Vendrell J, Aviles F, Fricker L, Coll M, et al. The crystal structure of the inhibitor-complexed carboxypeptidase D domain II and the modeling of regulatory carboxypeptidases. J Biol Chem. 2001;276:16177-84 pubmed
  26. Settle S, Green M, Burtis K. The silver gene of Drosophila melanogaster encodes multiple carboxypeptidases similar to mammalian prohormone-processing enzymes. Proc Natl Acad Sci U S A. 1995;92:9470-4 pubmed
    ..One class of svr mRNAs is alternatively spliced to encode at least two polyproteins, each of which is composed of two carboxypeptidase domains. ..
  27. Wiwanitkit V. Type I diabetes mellitus in human and chimpanzee: a comparison of kyoto encyclopedia of genes and genomes pathway. Diabetes Technol Ther. 2007;9:145-8 pubmed
    ..These results can imply a close relation between the human and the chimpanzee. They also confirm usage of the chimpanzee model for studies of type 1 diabetes pathophysiology. ..
  28. Shiraki T, Kondo S, Katayama S, Waki K, Kasukawa T, Kawaji H, et al. Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage. Proc Natl Acad Sci U S A. 2003;100:15776-81 pubmed
    ..The high-throughput nature of this technology paves the way for understanding gene networks via correlation of promoter usage and gene transcriptional factor expression. ..
  29. Leibel R, Chung W, Chua S. The molecular genetics of rodent single gene obesities. J Biol Chem. 1997;272:31937-40 pubmed
  30. Le Lay S, Krief S, Farnier C, Lefrere I, Le Liepvre X, Bazin R, et al. Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes. J Biol Chem. 2001;276:16904-10 pubmed
    ..This is the first evidence that intracellular cholesterol might serve as a link between fat cell size and adipocyte metabolic activity. ..
  31. Friis Hansen L, Rehfeld J. Impaired feedback of gastric functions in carboxypeptidase E-deficient mice. Biochem Biophys Res Commun. 2000;267:638-42 pubmed
    ..Furthermore, the synthesis of antral somatostatin and fundic chromogranin A is also abnormal. Hence the results suggest a breakdown in the feedback loop that regulates gastric acid secretion. ..
  32. Solov ev V, Gengin M, Solov eva O, Pavlova O, Lobzina E. Effect of cholinergic drugs on the activity of basic carboxypeptidases in rat nervous tissue. Biochemistry (Mosc). 2011;76:1172-7 pubmed publisher
    ..single administration of cholinergic drugs (arecoline, atropine, nicotine, mecamylamine) on the activity of carboxypeptidase H and of phenylmethylsulfonyl fluoride-inhibited carboxypeptidase, which are involved in metabolism of ..
  33. Weng S, Chang S, Cheng Y, Wang H, Wang T, Chang M, et al. Comparative transcriptome analysis reveals a fetal origin for mesenchymal stem cells and novel fetal surface antigens for noninvasive prenatal diagnosis. Taiwan J Obstet Gynecol. 2011;50:447-57 pubmed publisher
    ..The novel membrane proteins on the fetal MSC surface are promising candidate biomarkers for positively isolating fetal MSCs from maternal blood for noninvasive prenatal diagnosis. ..
  34. Wang J, Zhang Y, Yang Z, Zhu T, Wang L, Chen B, et al. Association of human carboxypeptidase E exon5 gene polymorphisms with angiographical characteristics of coronary atherosclerosis in a Chinese population. Acta Pharmacol Sin. 2008;29:736-44 pubmed publisher
    ..These findings indicate that the 801C>T polymorphism in the CPE exon5 gene may contribute to the angiographical characteristics of coronary atherosclerosis in the Chinese population. ..
  35. Lim K, Tyler C, Lim S, Giuliano R, Federoff H. Proteolytic processing of proNGF is necessary for mature NGF regulated secretion from neurons. Biochem Biophys Res Commun. 2007;361:599-604 pubmed
    ..These experiments demonstrate that hippocampal neurons harbor multiple pathways to process proNGF of which the furin consensus sequence is the preferred processing site. ..
  36. Zhang D, Zhou Z, Li L, Weng J, Huang G, Jing P, et al. Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes. Diabet Med. 2006;23:67-71 pubmed
    ..The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and ..
  37. Takeuchi T, Hosaka M. Sorting mechanism of peptide hormones and biogenesis mechanism of secretory granules by secretogranin III, a cholesterol-binding protein, in endocrine cells. Curr Diabetes Rev. 2008;4:31-8 pubmed
    ..Although the two models have been conflicting, we suggest that both are cooperative and compensating each other for the sorting of peptide hormones and the biogenesis of secretory granules. ..
  38. Helwig M, Vivoli M, Fricker L, Lindberg I. Regulation of neuropeptide processing enzymes by catecholamines in endocrine cells. Mol Pharmacol. 2011;80:304-13 pubmed publisher
  39. Yuan Q, Fontenele Neto J, Fricker L. Effect of voluntary exercise on genetically obese Cpefat/fat mice: quantitative proteomics of serum. Obes Res. 2004;12:1179-88 pubmed
    ..The serum proteomics results indicated that Cpefat/fat and wild-type mice differed in their response to exercise. ..
  40. Liu A, Shao C, Jin G, Liu R, Hao J, Shao Z, et al. Downregulation of CPE regulates cell proliferation and chemosensitivity in pancreatic cancer. Tumour Biol. 2014;35:12459-65 pubmed publisher
    ..Taken together, our results demonstrate that CPE plays an important role in pancreatic cancer. Inhibition of CPE may serve as a potential target for PC therapeutics. ..
  41. Che F, Fricker L. Quantitative peptidomics of mouse pituitary: comparison of different stable isotopic tags. J Mass Spectrom. 2005;40:238-49 pubmed
    ..In conclusion, both succinyl and TMAB isotopic labels are useful for quantitative peptidomics, and together these two labels provide more complete coverage of the endogenous peptides...
  42. Weiler R, Cidon S, Gershon M, Tamir H, Hogue Angeletti R, Winkler H. Adrenal chromaffin granules and secretory granules from thyroid parafollicular cells have several common antigens. FEBS Lett. 1989;257:457-9 pubmed
    ..Furthermore, six common membrane antigens were found: cytochrome b-561, carboxypeptidase H, glycoprotein II, glycoprotein III, synaptin/synaptophysin and SV 2...
  43. Vernigora A, Mikhaĭlova O, Gengin M, Ryzhkova I, Mukhina E. [Effect of chronic ethanol consumption on basic carboxypeptidase activity in regions of the rat brain]. Ukr Biokhim Zh (1999). 2002;74:128-30 pubmed
    It is discovered that chronic consumption of ethanol induced decrease of carboxypeptidase H activity in striatum by 27%; increase of carboxypeptidase M activity in hippocampus by 67% and decrease in cerebral hemispheres by 34%; ..
  44. Vernigora A, Gengin M, Mukhina E, Mikhaĭlova O. [Effect of chloroform and ether narcosis on the activity of basic carboxypeptidases in the hypothalamic-pituitary-adrenal axis in rats]. Ukr Biokhim Zh (1999). 2002;74:124-5 pubmed
    It is discovered that chloroform narcosis does not influence on carboxypeptidase H and phenylmethylsulfonyl fluoride-inhibited carboxypeptidase activity in the rats hypothalamic-pituitary-adrenal axis...
  45. 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. ..
  46. Varlamov O, Fricker L. The C-terminal region of carboxypeptidase E involved in membrane binding is distinct from the region involved with intracellular routing. J Biol Chem. 1996;271:6077-83 pubmed
    ..Taken together, these results indicate that the C-terminal 14 amino acids of CPE are important for membrane binding and that membrane binding and sorting require distinct signals. ..
  47. Jung Y, Kunczt C, Pearson R, Dixon J, Fricker L. Structural characterization of the rat carboxypeptidase-E gene. Mol Endocrinol. 1991;5:1257-68 pubmed
  48. Sekiguchi T, Kawashima T, Satou Y, Satoh N. Further EST analysis of endocrine genes that are preferentially expressed in the neural complex of Ciona intestinalis: receptor and enzyme genes associated with endocrine system in the neural complex. Gen Comp Endocrinol. 2007;150:233-45 pubmed
    ..These data provide the molecular basis for further functional studies of the endocrine role of the neural complex of ascidians. ..
  49. Cawley N, Rathod T, Young S, Lou H, Birch N, Loh Y. Carboxypeptidase E and Secretogranin III Coordinately Facilitate Efficient Sorting of Proopiomelanocortin to the Regulated Secretory Pathway in AtT20 Cells. Mol Endocrinol. 2016;30:37-47 pubmed publisher
    ..These results suggest that multiple sorting systems exist, providing redundancy to ensure the important task of continuous and accurate trafficking of prohormones to the granules of the RSP for the production of peptide hormones. ..
  50. Hougaard D, Larsson L. Carboxypeptidase E in rat antropyloric mucosa: distribution in progenitor and mature endocrine cell types. Histochem Cell Biol. 2004;121:55-61 pubmed
    ..These data indicate that immature G/D cells are able to process gastrin to glycine-extended forms and that CPE-mediated processing is not a characteristic of mature somatostatin and serotonin cells. ..
  51. Merkulova M, Huynh H, Radchenko V, Saito K, Lipkin V, Shuvaeva T, et al. Secretion of the mammalian Sec14p-like phosphoinositide-binding p45 protein. FEBS J. 2005;272:5595-605 pubmed
    ..Our findings suggest that p45 and phosphoinositides may participate in the formation of the protective mucus on nasal epithelium. ..
  52. Gomez P, Hallberg L, Greeley G. Carboxypeptidase E (CPE) deficiency in mice with the fat mutation have reduced stomach function. Proc Soc Exp Biol Med. 1999;220:52-3 pubmed
    ..Both gastric acid and challenged gastrin secretion are reduced in Cpefat/Cpefat mice. We conclude that stomach CPE activity is essential for gastric secretory activity and for challenged gastrin release. ..
  53. Song L, Fricker L. The pro region is not required for the expression or intracellular routeing of carboxypeptidase E. Biochem J. 1997;323 ( Pt 1):265-71 pubmed
    ..Taken together, these results suggest that the pro region of CPE is not required for the expression or intracellular routeing of this protein. ..
  54. Beinfeld M. Biosynthesis and processing of pro CCK: recent progress and future challenges. Life Sci. 2003;72:747-57 pubmed
    ..It also points out the major challenges that remain for future research. ..
  55. 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
    ..The results also showed that the artificial differentiation of RGC-5 or NS20Y cells was different from maturation of its corresponding normal tissue. ..
  56. Zhang H, Li S, Wang M, Vukusic B, Pristupa Z, Liu F. Regulation of dopamine transporter activity by carboxypeptidase E. Mol Brain. 2009;2:10 pubmed publisher
    ..Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity. ..
  57. Spiegelman B, Flier J. Adipogenesis and obesity: rounding out the big picture. Cell. 1996;87:377-89 pubmed
  58. Wei S, Feng Y, Che F, Pan H, Mzhavia N, Devi L, et al. Obesity and diabetes in transgenic mice expressing proSAAS. J Endocrinol. 2004;180:357-68 pubmed
    ..Taken together, these results are consistent with a role for proSAAS-derived peptides as neuropeptides that influence body weight independently of their function as inhibitors of prohormone convertase 1. ..
  59. Murthy S, Thouennon E, Li W, Cheng Y, Bhupatkar J, Cawley N, et al. Carboxypeptidase E protects hippocampal neurons during stress in male mice by up-regulating prosurvival BCL2 protein expression. Endocrinology. 2013;154:3284-93 pubmed publisher
    ..Thus, during mild CRS, CPE expression is up-regulated, possibly contributed by glucocorticoids, to mediate neuroprotection of the hippocampus by enhancing BCL2 expression through AKT signaling, and thereby maintaining allostasis. ..
  60. Vernigora A, Saldaev D, Gengin M. [Effect of testosterone and progesterone on carboxypeptidase H activity during stress in mice]. Ross Fiziol Zh Im I M Sechenova. 2002;88:1453-7 pubmed
    ..3 mg/kg of body weight) and progesterone (1 mg/kg of body weight) partially prevent an augmentation of the carboxypeptidase H activity in the mouse pituitary gland under stress caused by a single intraperitoneal administration of ..
  61. Carrel D, Du Y, Komlos D, Hadzimichalis N, Kwon M, Wang B, et al. NOS1AP regulates dendrite patterning of hippocampal neurons through a carboxypeptidase E-mediated pathway. J Neurosci. 2009;29:8248-58 pubmed publisher
    ..Together, our results suggest that NOS1AP-L plays an important role in the initiation, outgrowth, and maintenance of dendrites during development. ..
  62. 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 indicated by appearance of intermediate-sized processing products. ..
  63. Raghuraman G, Kalari A, Dhingra R, Prabhakar N, Kumar G. Enhanced neuropeptide Y synthesis during intermittent hypoxia in the rat adrenal medulla: role of reactive oxygen species-dependent alterations in precursor peptide processing. Antioxid Redox Signal. 2011;14:1179-90 pubmed publisher
  64. Rawdon B, Larsson L. Development of hormonal peptides and processing enzymes in the embryonic avian pancreas with special reference to co-localisation. Histochem Cell Biol. 2000;114:105-12 pubmed
  65. Cain B, Wang W, Beinfeld M. Cholecystokinin (CCK) levels are greatly reduced in the brains but not the duodenums of Cpe(fat)/Cpe(fat) mice: a regional difference in the involvement of carboxypeptidase E (Cpe) in pro-CCK processing. Endocrinology. 1997;138:4034-7 pubmed
    ..The Cpe(fat)/Cpe(fat) mouse phenotype obviously involves multiple endocrine defects, however, it is tempting to speculate that this severe CNS deficiency in CCK 8 may be related to the adult-onset obesity seen in this mutant mouse. ..
  66. Irminger J, Verchere C, Meyer K, Halban P. Proinsulin targeting to the regulated pathway is not impaired in carboxypeptidase E-deficient Cpefat/Cpefat mice. J Biol Chem. 1997;272:27532-4 pubmed
    ..CPE is thus not essential for sorting proinsulin to granules. ..
  67. Hall C, Manser E, Spurr N, Lim L. Assignment of the human carboxypeptidase E (CPE) gene to chromosome 4. Genomics. 1993;15:461-3 pubmed
  68. Skalka N, Caspi M, Caspi E, Loh Y, Rosin Arbesfeld R. Carboxypeptidase E: a negative regulator of the canonical Wnt signaling pathway. Oncogene. 2013;32:2836-47 pubmed publisher
  69. Parkinson D. Carboxypeptidase H in bovine pituitary gland: soluble forms are not processed at the C-terminus. Mol Cell Endocrinol. 1992;86:221-33 pubmed
    b>Carboxypeptidase H (CP-H) has been characterized in anterior and posterior lobes of bovine pituitary with regard to subcellular distribution, enzymatic properties, nature of membrane association, number of forms and C-terminal processing...
  70. Zhu X, Wu K, Rife L, Cawley N, Brown B, Adams T, et al. Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina. J Neurochem. 2005;95:1351-62 pubmed
    ..These results suggest that CPE is required for normal-sized photoreceptor synaptic terminal and normal signal transmission to the inner retina. ..
  71. Varlamov O, Fricker L, Furukawa H, Steiner D, Langley S, Leiter E. Beta-cell lines derived from transgenic Cpe(fat)/Cpe(fat) mice are defective in carboxypeptidase E and proinsulin processing. Endocrinology. 1997;138:4883-92 pubmed
    ..The secretion of insulin/proinsulin from NIT-2 and -3 cells is significantly elevated by secretagogues, indicating that CPE is not required for sorting proinsulin into the regulated pathway. ..
  72. Leiter E, Kintner J, Flurkey K, Beamer W, Naggert J. Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus. Endocrine. 1999;10:57-66 pubmed
  73. Ramis J, Franssen van Hal N, Kramer E, Llado I, Bouillaud F, Palou A, et al. Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects. Cell Mol Life Sci. 2002;59:1960-71 pubmed
    ..The involvement of CPE and THBS1 in obesity allows us to suggest that the physiological processes controlled by these genes contribute to depot and gender-related differences in the metabolic complications of obesity. ..
  74. Mousa S, Shakibaei M, Sitte N, Schafer M, Stein C. Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain. Endocrinology. 2004;145:1331-41 pubmed
    ..Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules. ..
  75. Chikuma T, Inomata Y, Tsuchida K, Hojo H, Kato T. Effect of monensin on the levels of tachykinins and their processing enzyme activity in rat dorsal root ganglia. Neurosci Lett. 2002;326:89-92 pubmed
    ..These data suggest that proteolytic processing enzymes may in part modulate the biological activity of neuropeptides within a trans-Golgi apparatus. ..
  76. Zhang X, Zhu J, Loh Y, Berghman L. Carboxypeptidase E, an essential element of the regulated secretory pathway, is expressed and partially co-localized with chromogranin A in chicken thymus. Cell Tissue Res. 2009;337:371-9 pubmed publisher
  77. Koshimizu H, Senatorov V, Loh Y, Gozes I. Neuroprotective protein and carboxypeptidase E. J Mol Neurosci. 2009;39:1-8 pubmed publisher
    ..Future studies will elucidate how these two versatile proteins converge onto a similar endpoint: neuroprotection. ..
  78. Rodriguiz R, Wilkins J, Creson T, Biswas R, Berezniuk I, Fricker A, et al. Emergence of anxiety-like behaviours in depressive-like Cpe(fat/fat) mice. Int J Neuropsychopharmacol. 2013;16:1623-34 pubmed publisher
    ..Since depressive-like responses in the Cpe(fat/fat) mice are rescued by 2 wk, but not acute, treatment with fluoxetine or bupropion, these mice may serve as a useful model that resembles human depression. ..
  79. Arnaoutova I, Jackson C, Al Awar O, Donaldson J, Loh Y. Recycling of Raft-associated prohormone sorting receptor carboxypeptidase E requires interaction with ARF6. Mol Biol Cell. 2003;14:4448-57 pubmed
    ..Thus, CPE recycles back to the TGN by a novel mechanism requiring ARF6 interaction and activity. ..