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Gene Review

Pcsk5  -  proprotein convertase subtilisin/kexin type 5

Rattus norvegicus

Synonyms: PC5, PC6, Pc5, Proprotein convertase 5, Proprotein convertase 6, ...
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Disease relevance of Pcsk5

  • The therapeutic indices (LD50-/ID90) for 2 against the ADJ/PC6 mouse tumor and the Walker 256 tumor in the rat were 28.6 and 7.7, respectively, and were lower than the corresponding values for 1 (91.8 and 33.2, respectively) although the toxicities toward Walker cells in a bioassay system of 1 and 2 following microsomal metabolism were similar [1].
  • Glucose administration in Sarcoma-180 and ADJ/PC6 tumour bearing animals did not alter the tumour intracellular pH determined in vivo indirectly from the distribution of the weak non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolinedione (DMO) between intra- and extra-cellular water [2].
  • We conclude that EA on bilateral PC6 (Neiguan) prevents and attenuates I/R injury to the heart, and that this approach may provide an applicable and preventative alternative for patients with ischemic heart disease [3].
  • Electroacupuncture on PC6 (Neiguan) attenuates ischemia/reperfusion injury in rat hearts [3].
  • The results showed that there were significant reductions in cardiac enzymes, the duration of arrhythmia and mortality rate in rats that were either preconditioned or treated with EA on PC6, compared with those that did not undergo EA on PC6 (P < 0.05) [3].

High impact information on Pcsk5

  • Furin and PC6 were weakly and evenly expressed in the entire islet [4].
  • Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly decreased dopamine release in the nucleus accumbens [5].
  • Coordinated regulation and colocalization of alphav integrin and its activating enzyme proprotein convertase PC5 in vivo [6].
  • Functional studies in mice established that blocking production of the CaBPs and PC6 within the endometrium completely prevented implantation and thus provided proof of principle that these molecules are potential contraceptive targets [7].
  • Needlepoints corresponded to Shaohai (HT3) and Neiguan (PC6) on the heart and pericardium channel [8].

Biological context of Pcsk5


Anatomical context of Pcsk5

  • Proprotein convertase PC5 regulation by PDGF-BB involves PI3-kinase/p70(s6)-kinase activation in vascular smooth muscle cells [10].
  • The two isoforms of PC-6 have different patterns of distribution in the gastrointestinal tract and pancreas, suggesting that they process proforms of different gut peptides [11].
  • The magnitude of the deuterium isotope effect (kH/kD) associated with appropriate C-deuteration has been related to antitumor activity against the ADJ/PC6 murine plasma cell tumor [12].
  • Before the experiment, EA was applied at bilateral Neiguan acupoints (PC6) in the forelimbs in EA and EAP groups for 30 min once a day for 3 consecutive days [13].
  • The aim of this study was to test the hypothesis that through somato-visceral regulation, ischemia-reperfusion (I/R) injury to the myocardium can be avoided by electroacupuncture (EA) on PC6 (Neiguan) [3].

Associations of Pcsk5 with chemical compounds

  • Electroacupuncture at HT3 and PC6 points but not at control points (TE5, LI11, and tail) significantly reduced the expected increases in BP, HR, and attenuated plasma levels of NE and EPI in response to 3 h of immobilization stress [8].
  • The uptake of 67Ga-citrate in the tissues of the mouse and rat and in two mouse tumours, S180 and PC6, has been measured and shown to be independent of the citrate concentration of the injection dose [14].

Analytical, diagnostic and therapeutic context of Pcsk5

  • Electroacupuncture on PC6 (Neiguan) was brought about by the application of metal needles over the bilateral median nerve at a point 1.5 cm proximal to the palm crease in male Spraque-Dawley rats [3].
  • Intratumoral levels of beta-glucoronidase occurring in DMBA-induced tumors 4 days after ovariectomy were found to be similar to those in the aniline mustard-sensitive mouse plasma cell tumor ADJ/PC6 [15].


  1. Synthesis and antitumor activity of 6-trifluoromethylcyclophosphamide and related compounds. Farmer, P.B., Cox, P.J. J. Med. Chem. (1975) [Pubmed]
  2. Cytotoxicity of aniline mustard glucuronide alone or in a combination with glucose in Walker cells in culture and sarcoma-180 tumour bearing animals. Deliconstantinos, G., Ramantanis, G., Todorou, D.K. Biomed. Pharmacother. (1983) [Pubmed]
  3. Electroacupuncture on PC6 (Neiguan) attenuates ischemia/reperfusion injury in rat hearts. Tsou, M.T., Huang, C.H., Chiu, J.H. Am. J. Chin. Med. (2004) [Pubmed]
  4. Distribution of the Kexin family proteases in pancreatic islets: PACE4C is specifically expressed in B cells of pancreatic islets. Nagamune, H., Muramatsu, K., Akamatsu, T., Tamai, Y., Izumi, K., Tsuji, A., Matsuda, Y. Endocrinology (1995) [Pubmed]
  5. Acupuncture-mediated inhibition of ethanol-induced dopamine release in the rat nucleus accumbens through the GABAB receptor. Yoon, S.S., Kwon, Y.K., Kim, M.R., Shim, I., Kim, K.J., Lee, M.H., Lee, Y.S., Golden, G.T., Yang, C.H. Neurosci. Lett. (2004) [Pubmed]
  6. Coordinated regulation and colocalization of alphav integrin and its activating enzyme proprotein convertase PC5 in vivo. Stawowy, P., Graf, K., Goetze, S., Roser, M., Chrétien, M., Seidah, N.G., Fleck, E., Marcinkiewicz, M. Histochem. Cell Biol. (2003) [Pubmed]
  7. Identification of novel endometrial targets for contraception. Nie, G., Findlay, J.K., Salamonsen, L.A. Contraception. (2005) [Pubmed]
  8. Effect of electroacupuncture on response to immobilization stress. Yang, C.H., Lee, B.B., Jung, H.S., Shim, I., Roh, P.U., Golden, G.T. Pharmacol. Biochem. Behav. (2002) [Pubmed]
  9. Endoproteolytic activation of alpha(v) integrin by proprotein convertase PC5 is required for vascular smooth muscle cell adhesion to vitronectin and integrin-dependent signaling. Stawowy, P., Kallisch, H., Veinot, J.P., Kilimnik, A., Prichett, W., Goetze, S., Seidah, N.G., Chrétien, M., Fleck, E., Graf, K. Circulation (2004) [Pubmed]
  10. Proprotein convertase PC5 regulation by PDGF-BB involves PI3-kinase/p70(s6)-kinase activation in vascular smooth muscle cells. Stawowy, P., Blaschke, F., Kilimnik, A., Goetze, S., Kallisch, H., Chrétien, M., Marcinkiewicz, M., Fleck, E., Graf, K. Hypertension (2002) [Pubmed]
  11. Distribution of prohormone convertase-6 expression in the gastrointestinal tract and effects of a fasting-refeeding regimen and a high-fat diet on ileal prohormone convertase-6 expression. Udupi, V., Gomez, G., Lambertz, I., Qi, X., Reed, J., Greeley, G.H. Endocrine (1997) [Pubmed]
  12. The use of deuterated analogs in qualitative and quantitative investigations of the metabolism of cyclophosphamide (NSC-26271). Cox, P.J., Farmer, P.B., Foster, A.B., Gilby, E.D., Jarman, M. Cancer treatment reports. (1976) [Pubmed]
  13. A Preliminary Study on the Cardioprotection of Acupuncture Pretreatment in Rats with Ischemia and Reperfusion: Involvement of Cardiac beta-Adrenoceptors. Gao, J., Fu, W., Jin, Z., Yu, X. The journal of physiological sciences : JPS. (2006) [Pubmed]
  14. The relationship of 67Ga uptake to citrate dose, compared with 67Ga-chloride and 67Ga-transferrin in rodent tissues and tumours. Hammersley, P.A., Zivanovic, M.A. Nuklearmedizin. (1980) [Pubmed]
  15. Enhanced cytostatic effectiveness of aniline mustard against 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors during regression in response to ovariectomy. Benckhuysen, C., Ter Hart, H.G., Van Dijk, P.J. Cancer treatment reports. (1981) [Pubmed]
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