cystinyl aminopeptidase


Summary: A zinc-containing sialoglycoprotein that is used to study aminopeptidase activity in the pathogenesis of hypertension. EC

Top Publications

  1. Katagiri H, Asano T, Yamada T, Aoyama T, Fukushima Y, Kikuchi M, et al. Acyl-coenzyme A dehydrogenases are localized on GLUT4-containing vesicles via association with insulin-regulated aminopeptidase in a manner dependent on its dileucine motif. Mol Endocrinol. 2002;16:1049-59 pubmed
  2. Rogi T, Tsujimoto M, Nakazato H, Mizutani S, Tomoda Y. Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. J Biol Chem. 1996;271:56-61 pubmed
    ..These results suggest that the enzyme is synthesized as an integral membrane protein and is released into blood under some physiological conditions. ..
  3. Abel E, Graveleau C, Betuing S, Pham M, Reay P, Kandror V, et al. Regulation of insulin-responsive aminopeptidase expression and targeting in the insulin-responsive vesicle compartment of glucose transporter isoform 4-deficient cardiomyocytes. Mol Endocrinol. 2004;18:2491-501 pubmed
    ..Thus, GLUT4 and IRAP content of early endosome-derived sorting vesicles and of IRVs are coordinately regulated, and both proteins are required for maintenance of key constituents of these compartments in cardiac muscle cells in vivo. ..
  4. Axén A, Lindeberg G, Demaegdt H, Vauquelin G, Karlen A, Hallberg M. Cyclic insulin-regulated aminopeptidase (IRAP)/AT4 receptor ligands. J Pept Sci. 2006;12:705-13 pubmed
    ..The cyclic constrained analogs allowed us to propose a tentative bioactive conformation of angiotensin IV and it seems that the peptide adopts an inverse gamma-turn at the C-terminal. ..
  5. Yeh T, Sbodio J, Tsun Z, Luo B, Chi N. Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase. Biochem J. 2007;402:279-90 pubmed
    ..Collectively, these findings suggest that physiological GSV trafficking depends in part on the presence of IRAP in these vesicles, and that this process is regulated by tankyrase and probably its PARP activity. ..
  6. Ye S, Chai S, Lew R, Albiston A. Insulin-regulated aminopeptidase: analysis of peptide substrate and inhibitor binding to the catalytic domain. Biol Chem. 2007;388:399-403 pubmed
  7. Mizutani S, Tomoda Y. Effects of placental proteases on maternal and fetal blood pressure in normal pregnancy and preeclampsia. Am J Hypertens. 1996;9:591-7 pubmed
    ..Placental proteases play important roles in controlling fetal and maternal blood pressure through regulation of the concentration of vasoactive peptides in the interface (placenta) between fetus and mother. ..
  8. Nakada T, Russell J, Wellman H, Boyd J, Nakada E, Thain K, et al. Leucyl/cystinyl aminopeptidase gene variants in septic shock. Chest. 2011;139:1042-1049 pubmed publisher
    ..genes (arginine vasopressin [AVP], arginine vasopressin receptor 1A and 1B [AVPR1A, AVPR1B], leucyl/cystinyl aminopeptidase [LNPEP], and oxytocin receptor [OXTR]), rs18059 in LNPEP (also known as vasopressinase) was associated ..
  9. Laeremans H, Demaegdt H, De Backer J, Le M, Kersemans V, Michotte Y, et al. Metal ion modulation of cystinyl aminopeptidase. Biochem J. 2005;390:351-7 pubmed
    b>Cystinyl aminopeptidase has one Zn2+-binding motif and is a member of the M1 aminopeptidase family...

More Information


  1. Takeuchi M, Itakura A, Okada M, Mizutani S, Kikkawa F. Impaired insulin-regulated membrane aminopeptidase translocation to the plasma membrane in adipocytes of Otsuka Long Evans Tokushima Fatty rats. Nagoya J Med Sci. 2006;68:155-63 pubmed
    ..Continuous measurement of cell surface IRAP activity allowed accurate evaluations of GLUT4/IRAP vesicle translocation and of the establishment of defects in OLETF rats. ..
  2. Fernando R, Larm J, Albiston A, Chai S. Distribution and cellular localization of insulin-regulated aminopeptidase in the rat central nervous system. J Comp Neurol. 2005;487:372-90 pubmed
  3. Larance M, Ramm G, St ckli J, van Dam E, Winata S, Wasinger V, et al. Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking. J Biol Chem. 2005;280:37803-13 pubmed publisher
    ..These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4...
  4. Demaegdt H, Laeremans H, De Backer J, Mosselmans S, Le M, Kersemans V, et al. Synergistic modulation of cystinyl aminopeptidase by divalent cation chelators. Biochem Pharmacol. 2004;68:893-900 pubmed
    ..CHO-K1) cells were used to study the opposite modulation of enzyme activity and [125I]Ang IV binding to cystinyl aminopeptidase (EC by divalent cation chelators...
  5. Albiston A, Mustafa T, McDowall S, Mendelsohn F, Lee J, Chai S. AT4 receptor is insulin-regulated membrane aminopeptidase: potential mechanisms of memory enhancement. Trends Endocrinol Metab. 2003;14:72-7 pubmed
    ..Here, we explore the potential mechanisms by which Ang IV binding to IRAP leads to the facilitation of learning and memory. ..
  6. Albiston A, Peck G, Yeatman H, Fernando R, Ye S, Chai S. Therapeutic targeting of insulin-regulated aminopeptidase: heads and tails?. Pharmacol Ther. 2007;116:417-27 pubmed
    ..This protein appears to have multiple physiological roles that are tissue- and domain-specific; thus the protein can be specifically targeted for treating different clinical conditions. ..
  7. Matsumoto H, Nagasaka T, Hattori A, Rogi T, Tsuruoka N, Mizutani S, et al. Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides. Eur J Biochem. 2001;268:3259-66 pubmed
    ..In addition, P-LAP was shown to degrade several bioactive neuropeptides such as Met-enkephalin and dynorphin A (1-8). These results suggest that P-LAP plays an important role in the regulation of neuronal cell function in the brain. ..
  8. Larrinaga G, Lopez J, Casis L, Blanco L, Gil J, Agirregoitia E, et al. Cystinyl aminopeptidase activity is decreased in renal cell carcinomas. Regul Pept. 2007;144:56-61 pubmed
    ..These data may open additional possibilities in the study of renal cell carcinoma with regard to the prognosis of patients. ..
  9. Kobayashi H, Mitsui T, Nomura S, Ohno Y, Kadomatsu K, Muramatsu T, et al. Expression of glucose transporter 4 in the human pancreatic islet of Langerhans. Biochem Biophys Res Commun. 2004;314:1121-5 pubmed
    ..This study provides the first evidence that GLUT4 is present in human and rat pancreatic islets and may suggest its specific role in glucose homeostasis in conjunction with IRAP/P-LAP. ..
  10. Siebelmann M, Wensing J, Verspohl E. The impact of ANG II and IV on INS-1 cells and on blood glucose and plasma insulin. J Recept Signal Transduct Res. 2010;30:234-45 pubmed publisher
    ..Effects are mediated by insulin release, which is accompanied by an influx of extracellular Ca(2+). The impact of ANG IV/IRAP agonists may be worth being used as antidiabetics. ..
  11. Albiston A, Morton C, Ng H, Pham V, Yeatman H, Ye S, et al. Identification and characterization of a new cognitive enhancer based on inhibition of insulin-regulated aminopeptidase. FASEB J. 2008;22:4209-17 pubmed publisher
    ..Notably, this study also provides unequivocal proof of principal that inhibition of IRAP results in memory enhancement. ..
  12. Jiang L, Fan J, Bai L, Wang Y, Chen Y, Yang L, et al. Direct quantification of fusion rate reveals a distal role for AS160 in insulin-stimulated fusion of GLUT4 storage vesicles. J Biol Chem. 2008;283:8508-16 pubmed
  13. Albiston A, McDowall S, Matsacos D, Sim P, Clune E, Mustafa T, et al. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem. 2001;276:48623-6 pubmed
    ..We have therefore demonstrated that the AT(4) receptor is IRAP and propose that AT(4) receptor ligands may exert their effects by inhibiting the catalytic activity of IRAP thereby extending the half-life of its neuropeptide substrates. ..
  14. Jiang H, Li J, Katz E, Charron M. GLUT4 ablation in mice results in redistribution of IRAP to the plasma membrane. Biochem Biophys Res Commun. 2001;284:519-25 pubmed
    ..We propose the compartment containing IRAP and proteins normally associated with GLUT4 vesicle traffics constitutively to the cell surface in GLUT4 null adipocytes and skeletal muscle. ..
  15. Keller S, Davis A, Clairmont K. Mice deficient in the insulin-regulated membrane aminopeptidase show substantial decreases in glucose transporter GLUT4 levels but maintain normal glucose homeostasis. J Biol Chem. 2002;277:17677-86 pubmed
    ..The absence of IRAP does not affect the subcellular distribution of GLUT4 in adipocytes. However, it leads to substantial decreases in GLUT4 expression. ..
  16. Carvalho E, Schellhorn S, Zabolotny J, Martin S, Tozzo E, Peroni O, et al. GLUT4 overexpression or deficiency in adipocytes of transgenic mice alters the composition of GLUT4 vesicles and the subcellular localization of GLUT4 and insulin-responsive aminopeptidase. J Biol Chem. 2004;279:21598-605 pubmed
    ..Our results show that GLUT4 overexpression or deficiency affects the amount of other GLUT4-vesicle proteins including IRAP and VAMP2 and that GLUT4 sequestration is saturable. ..
  17. Kondo C, Shibata K, Terauchi M, Kajiyama H, Ino K, Nomura S, et al. A novel role for placental leucine aminopeptidase (P-LAP) as a determinant of chemoresistance in endometrial carcinoma cells. Int J Cancer. 2006;118:1390-4 pubmed
    ..These results suggest that P-LAP reduces sensitivity to anticancer drugs via inhibition of mitochondria-mediated apoptosis, and may be a molecular target for conquering anticancer drug resistance. ..
  18. Hou J, Suzuki N, Pessin J, Watson R. A specific dileucine motif is required for the GGA-dependent entry of newly synthesized insulin-responsive aminopeptidase into the insulin-responsive compartment. J Biol Chem. 2006;281:33457-66 pubmed
    ..Taken together, these data indicate that LL(76,77) functions during the GGA-dependent sorting of newly made IRAP into the insulin-responsive storage compartment. ..
  19. Albiston A, Pederson E, Burns P, Purcell B, Wright J, Harding J, et al. Attenuation of scopolamine-induced learning deficits by LVV-hemorphin-7 in rats in the passive avoidance and water maze paradigms. Behav Brain Res. 2004;154:239-43 pubmed
    ..These studies clearly demonstrate that LVV-H7, like Ang IV, is a pharmacologically active AT(4) ligand that attenuates the deleterious effects of scopolamine on learning performance in two different behavioral paradigms. ..
  20. Wong Y, Sim M, Lee K. Des-aspartate-angiotensin-I and angiotensin IV improve glucose tolerance and insulin signalling in diet-induced hyperglycaemic mice. Biochem Pharmacol. 2011;82:1198-208 pubmed publisher
    ..DAA-I acts via the angiotensin AT(1) receptor and activates the insulin pathway. Ang-IV acts via IRAP, which couples PI3K and activates the later part of the insulin pathway. ..
  21. Shibata K, Kikkawa F, Suzuki Y, Mizokami Y, Kajiyama H, Ino K, et al. Expression of placental leucine aminopeptidase is associated with a poor outcome in endometrial endometrioid adenocarcinoma. Oncology. 2004;66:288-95 pubmed
    ..This study investigated whether the expression of P-LAP correlates with clinicopathologic factors and prognosis in patients with endometrial endometrioid adenocarcinoma...
  22. Demaegdt H, Lenaerts P, Swales J, De Backer J, Laeremans H, Le M, et al. Angiotensin AT4 receptor ligand interaction with cystinyl aminopeptidase and aminopeptidase N: [125I]Angiotensin IV only binds to the cystinyl aminopeptidase apo-enzyme. Eur J Pharmacol. 2006;546:19-27 pubmed
    Due to its high affinity for [(125)I]Angiotensin IV, cystinyl aminopeptidase (CAP) has recently been assigned as the 'angiotensin AT(4) receptor'...
  23. Saveanu L, Carroll O, Weimershaus M, Guermonprez P, Firat E, Lindo V, et al. IRAP identifies an endosomal compartment required for MHC class I cross-presentation. Science. 2009;325:213-7 pubmed publisher
    ..We propose the existence of two pathways for proteasome-dependent cross-presentation in which final peptide trimming involves IRAP in endosomes and involves the related aminopeptidases in the endoplasmic reticulum. ..
  24. Jedrychowski M, Gartner C, Gygi S, Zhou L, Herz J, Kandror K, et al. Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important vesicle component and target of insulin signaling. J Biol Chem. 2010;285:104-14 pubmed publisher
    ..Furthermore, adipose-specific LRP1 knock-out mice also exhibit decreased GLUT4 expression. These findings suggest LRP1 is an important component of GSVs, and its expression is needed for the formation of fully functional GSVs...
  25. Peck G, Ye S, Pham V, Fernando R, Macaulay S, Chai S, et al. Interaction of the Akt substrate, AS160, with the glucose transporter 4 vesicle marker protein, insulin-regulated aminopeptidase. Mol Endocrinol. 2006;20:2576-83 pubmed
    ..We hypothesize that AS160 is localized to GLUT4-containing vesicles via its interaction with IRAP where it inhibits the activity of Rab substrates in its vicinity, effectively tethering the vesicles intracellularly. ..
  26. Liao H, Keller S, Castle J. Insulin-regulated aminopeptidase marks an antigen-stimulated recycling compartment in mast cells. Traffic. 2006;7:155-67 pubmed
    ..We propose that IRAP vesicles represent a second IgE-sensitive exocytotic compartment in mast cells, which is regulated differently from secretory granules, and that these vesicles may be similar to GLUT4 vesicles. ..
  27. Ishii M, Naruse K, Hattori A, Tsujimoto M, Ishiura S, Numaguchi Y, et al. Oxytocin hypersensitivity in pregnant P-LAP deficient mice. Life Sci. 2009;84:668-72 pubmed publisher
    ..P-LAP might be involved in the increased OT sensitivity just prior to onset of labor and also in the onset of labor by degradation of OT. ..
  28. Wallis M, Lankford M, Keller S. Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP. Am J Physiol Endocrinol Metab. 2007;293:E1092-102 pubmed
    ..Changes in plasma and brain vasopressin levels in IRAP(-/-) mice suggest a significant role for IRAP in regulating vasopressin. We have also uncovered a novel IRAP-dependent insulin effect: to acutely modify vasopressin. ..
  29. Keller S, Scott H, Mastick C, Aebersold R, Lienhard G. Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles. J Biol Chem. 1995;270:23612-8 pubmed
  30. Tsujimoto M, Mizutani S, Adachi H, Kimura M, Nakazato H, Tomoda Y. Identification of human placental leucine aminopeptidase as oxytocinase. Arch Biochem Biophys. 1992;292:388-92 pubmed
    ..These results suggest that P-LAP shows oxytocinase activity and plays an important role in the regulation of the plasma level of these hormones during pregnancy. ..
  31. Kobayashi H, Nomura S, Mitsui T, Ito T, Kuno N, Ohno Y, et al. Tissue distribution of placental leucine aminopeptidase/oxytocinase during mouse pregnancy. J Histochem Cytochem. 2004;52:113-21 pubmed
    ..Therefore, P-LAP may play a significant role in various physiological processes in non-pregnant, pregnant, and fetal mice. ..
  32. Lew R, Mustafa T, Ye S, McDowall S, Chai S, Albiston A. Angiotensin AT4 ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP). J Neurochem. 2003;86:344-50 pubmed
    ..We propose that the physiological effects of AT4 ligands result, in part, from inhibition of IRAP cleavage of neuropeptides involved in memory processing. ..
  33. Klimek M, Wicherek L, Popiela T, Skotniczny K, Tomaszewska B. Changes of maternal ACTH and oxytocinase plasma concentrations during the first trimester of spontaneous abortion. Neuro Endocrinol Lett. 2005;26:342-6 pubmed
    ..The observed ACTH rise during spontaneous abortion might be also related to the alterations at the maternal-fetal interface and the response of HPA axis to the growing cytotoxic activity. ..
  34. Jordens I, Molle D, Xiong W, Keller S, McGraw T. Insulin-regulated aminopeptidase is a key regulator of GLUT4 trafficking by controlling the sorting of GLUT4 from endosomes to specialized insulin-regulated vesicles. Mol Biol Cell. 2010;21:2034-44 pubmed publisher
    ..In sum, we show that IRAP is both cargo and a key regulator of the insulin-regulated pathway. ..
  35. Chi N, Lodish H. Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. J Biol Chem. 2000;275:38437-44 pubmed
    ..We speculate that tankyrase may be involved in the long term effect of the MAPK cascade on the metabolism of GLUT4 vesicles. ..
  36. Kozaki H, Itakura A, Okamura M, Ohno Y, Wakai K, Mizutani S. Maternal serum placental leucine aminopeptidase (P-LAP)/oxytocinase and preterm delivery. Int J Gynaecol Obstet. 2001;73:207-13 pubmed
    ..Maternal serum P-LAP activity decreases in cases with spontaneous preterm delivery and may be a clinically potential marker for some cases of preterm labor. ..
  37. Wicherek L, Dutsch Wicherek M, Mak P, Klimek M. The Role of RCAS1 and oxytocinase in immune tolerance during pregnancy. Fetal Diagn Ther. 2005;20:420-5 pubmed
    ..Therefore, we posit that RCAS1 and CAP may play a role in the downregulation of the maternal immune response during pregnancy and may participate in the initiation of the labor. ..
  38. Shibata K, Kikkawa F, Kondo C, Mizokami Y, Kajiyama H, Ino K, et al. Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma. Gynecol Oncol. 2004;95:307-13 pubmed
    ..2- and 5.1-fold rates of apoptosis, respectively, compared to that of without treatment. P-LAP was suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma. ..
  39. Suzuki Y, Shibata K, Kikkawa F, Kajiyama H, Ino K, Nomura S, et al. Possible role of placental leucine aminopeptidase in the antiproliferative effect of oxytocin in human endometrial adenocarcinoma. Clin Cancer Res. 2003;9:1528-34 pubmed
    ..These findings suggested that P-LAP might be functionally positive on carcinoma cell growth by degrading suppressive peptides such as OT. ..
  40. Briet J. Diabetes insipidus, Sheehan's syndrome and pregnancy. Eur J Obstet Gynecol Reprod Biol. 1998;77:201-3 pubmed
    ..If DI occurs during pregnancy it may be the first manifestation of a latent central DI, which is often idiopathic, but rarely the first symptom of a pituitary or hypothalamic abnormality. It may also be part of Sheehan's syndrome. ..
  41. Stragier B, Demaegdt H, De Bundel D, Smolders I, Sarre S, Vauquelin G, et al. Involvement of insulin-regulated aminopeptidase and/or aminopeptidase N in the angiotensin IV-induced effect on dopamine release in the striatum of the rat. Brain Res. 2007;1131:97-105 pubmed
    ..We therefore hypothesize that the effect of angiotensin IV on dopamine release in the striatum is mediated via activation of IRAP and/or AP-N, possibly acting as receptors for angiotensin IV. ..
  42. Mustafa T, Chai S, May C, Mendelsohn F, Albiston A. Oxytocinase/insulin-regulated aminopeptidase is distributed throughout the sheep, female reproductive tract and is regulated by oestrogen in the uterus. Regul Pept. 2004;122:85-9 pubmed
    ..05) in the level of IRAP in the outer myometrium. These findings indicate an important role for IRAP in reproductive physiology in regulating the action of peptide hormones. ..
  43. Demaegdt H, De Backer J, Lukaszuk A, Toth G, Szemenyei E, Tourwe D, et al. Angiotensin IV displays only low affinity for native insulin-regulated aminopeptidase (IRAP). Fundam Clin Pharmacol. 2012;26:194-7 pubmed publisher
    ..By using 7B along with the new stable Ang IV-analog [(3) H]AL-11, we here show that the native enzyme is only a low-affinity target for Ang IV. ..
  44. Silveira P, Irazusta J, Gil J, Agirregoitia N, Casis L. Interactions among challenges of hydromineral balance, angiotensin-converting enzyme, and cystine aminopeptidase. Peptides. 2001;22:2137-44 pubmed
  45. Sugawara R, Lee E, Jang M, Jeun E, Hong C, Kim J, et al. Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist. J Exp Med. 2016;213:555-67 pubmed publisher
    ..Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. ..
  46. Chanson P, Salenave S. Diabetes insipidus and pregnancy. Ann Endocrinol (Paris). 2016;77:135-8 pubmed publisher
    ..Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted. ..
  47. Segarra A, Arechaga G, Prieto I, Ramírez Expósito M, Martinez Martos J, Ramirez M, et al. Effects of dietary supplementation with fish oil, lard, or coconut oil on oxytocinase activity in the testis of mice. Arch Androl. 2002;48:233-6 pubmed
    ..g., fish oil) in the diet may improve the fertilizing ability in mammals. Cystinyl aminopeptidase (oxytocinase) activity plays a major role regulating the functional status of OT...
  48. Ofner L, Hooper N. Ectodomain shedding of cystinyl aminopeptidase from human placental membranes. Placenta. 2002;23:65-70 pubmed
    b>Cystinyl aminopeptidase (CAP; EC is an integral protein of the placental membrane that is also found in a soluble form in maternal serum during pregnancy...
  49. Itoh C, Watanabe M, Nagamatsu A, Soeda S, Kawarabayashi T, Shimeno H. Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta: purification and characterization. Biol Pharm Bull. 1997;20:20-4 pubmed
    ..Thus, the two enzymes are quite distinct in their molecular nature and biochemical properties. They may play a regulatory role in the metabolism of oxytocin and other biologically active peptides in intact placenta. ..
  50. Illán Cabeza N, García García A, Martínez Martos J, Ramírez Expósito M, Moreno Carretero M. Antiproliferative effects of palladium(II) complexes of 5-nitrosopyrimidines and interactions with the proteolytic regulatory enzymes of the renin-angiotensin system in tumoral brain cells. J Inorg Biochem. 2013;126:118-27 pubmed publisher
  51. Iwase A, Nomura S, Mizutani S. Characterization of a secretase activity for placental leucine aminopeptidase. Arch Biochem Biophys. 2001;393:163-9 pubmed
    ..On the contrary, the distance to cleavage site showed no relation to P-LAP secretion. These results suggest that P-LAP secretase has a metalloprotease activity which depends on the amino acid sequence of the cleavage site. ..
  52. Zervoudi E, Saridakis E, Birtley J, Seregin S, Reeves E, Kokkala P, et al. Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses. Proc Natl Acad Sci U S A. 2013;110:19890-5 pubmed publisher
    ..This class of inhibitors constitutes a promising tool for controlling the cellular adaptive immune response in humans by modulating the antigen processing and presentation pathway. ..
  53. Cohen M, Wuillemin C, Chai S, Bischof P. Effects of ligands or substrate of insulin-regulated aminopeptidase (IRAP) on trophoblast invasion. J Pept Sci. 2008;14:883-7 pubmed publisher
    ..The peptide IRAP inhibitors could exert their effect on cytotrophoblastic cell invasiveness by inhibition of its enzymatic activity, and thus increasing half life of the known placental peptide substrate of IRAP, OT. ..
  54. Ikoma Y, Nomura S, Ito T, Katsumata Y, Nakata M, Iwanaga K, et al. Interleukin-1beta stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells. Mol Hum Reprod. 2003;9:103-10 pubmed
    ..These findings indicated that prolonged exposure to IL-1beta induces P-LAP in the trophoblasts, possibly via other de-novo protein synthesis, which contradicted our initial hypothesis. ..
  55. Chai S, Fernando R, Peck G, Ye S, Mendelsohn F, Jenkins T, et al. The angiotensin IV/AT4 receptor. Cell Mol Life Sci. 2004;61:2728-37 pubmed
  56. Nomura S, Ito T, Yamamoto E, Sumigama S, Iwase A, Okada M, et al. Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy. Biochim Biophys Acta. 2005;1751:19-25 pubmed
    ..P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as OT and vasopressin. ..
  57. Lukaszuk A, Demaegdt H, Feytens D, Vanderheyden P, Vauquelin G, Tourwe D. The replacement of His(4) in angiotensin IV by conformationally constrained residues provides highly potent and selective analogues. J Med Chem. 2009;52:5612-8 pubmed publisher
  58. Demaegdt H, Lukaszuk A, De Buyser E, De Backer J, Szemenyei E, Toth G, et al. Selective labeling of IRAP by the tritiated AT(4) receptor ligand [3H]Angiotensin IV and its stable analog [3H]AL-11. Mol Cell Endocrinol. 2009;311:77-86 pubmed publisher
    ..This confirms that the active and apo-forms of IRAP have a distinct pharmacological profile. ..
  59. Carrera González M, Ramírez Expósito M, de Saavedra J, Sánchez Agesta R, Mayas M, Martínez Martos J. Hypothalamus-pituitary-thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system. Tumour Biol. 2011;32:543-9 pubmed publisher
    ..Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption. ..
  60. Carrera M, Ramírez Expósito M, Valenzuela M, Garcia M, Mayas M, Martinez Martos J. Serum oxytocinase activity is related to tumor growth parameters in N-methyl nitrosourea induced rat breast cancer. Life Sci. 2004;75:1369-77 pubmed
    ..Our results confirm the involvement of OT in carcinogenesis and suggest a mayor role for oxytocinase activity in the development of breast cancer. ..
  61. Albiston A, Ye S, Chai S. Membrane bound members of the M1 family: more than aminopeptidases. Protein Pept Lett. 2004;11:491-500 pubmed
    ..In addition to their capacity to degrade a range of peptides a number of these aminopeptidases have novel functions that impact on cell signalling and will be discussed. ..
  62. Mpakali A, Saridakis E, Harlos K, Zhao Y, Kokkala P, Georgiadis D, et al. Ligand-Induced Conformational Change of Insulin-Regulated Aminopeptidase: Insights on Catalytic Mechanism and Active Site Plasticity. J Med Chem. 2017;60:2963-2972 pubmed publisher
    ..This conformation provides insight on IRAP's catalytic cycle and reveals significant active-site plasticity that may underlie its substrate permissiveness. ..
  63. Malide D, St Denis J, Keller S, Cushman S. Vp165 and GLUT4 share similar vesicle pools along their trafficking pathways in rat adipose cells. FEBS Lett. 1997;409:461-8 pubmed
    ..These data are consistent with the presence of a distinct insulin-sensitive compartment that sequesters both GLUT4 and vp165 and suggest similar trafficking routes through the recycling compartments. ..
  64. Ito T, Nomura S, Okada M, Katsumata Y, Iwase A, Kikkawa F, et al. Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene. Mol Hum Reprod. 2001;7:887-94 pubmed
    ..Our findings suggest that AP-2 may be one of the important factors regulating P-LAP gene expression in human placenta. ..
  65. Klimek M, Tomaszewska B. [Influence of ACTH-depot doses on neuroendocrine gestosis treatment]. Ginekol Pol. 2006;77:110-6 pubmed
    ..serum prelabour oxitocinase levels were precise factors of clinical results. ..