Endoproteolytic processing of proopiomelanocortin and prohormone convertases 1 and 2 in neuroendocrine cells overexpressing prohormone convertases 1 or 2
- PMID: 8021247
Endoproteolytic processing of proopiomelanocortin and prohormone convertases 1 and 2 in neuroendocrine cells overexpressing prohormone convertases 1 or 2
Abstract
AtT-20 mouse corticotrope tumor cell lines overexpressing the prohormone convertases PC1 or PC2 were established and used to examine prohormone and prohormone convertase biosynthetic processing. On a molar basis, wild-type AtT-20 cells synthesize about 20% as much PC1 as the endogenous prohormone, proopiomelanocortin (POMC). Kinetic, oligosaccharide, and temperature blockade analyses established that proPC1 is converted to PC1 in the endoplasmic reticulum at a rate independent of the level of PC1 or PC2 expression. In contrast, proPC2 is converted to PC2 primarily in a post-trans-Golgi compartment. PC1 is further shortened from its COOH-terminal end in a post-trans-Golgi compartment in a step that is accelerated at higher levels of PC1 expression, but unaltered by PC2 overexpression. The initial steps in POMC processing are speeded up by overexpression of PC1, and overexpression of PC1 leads to more extensive cleavage of POMC to smaller products. However, even when the rate of PC1 synthesis exceeds that for POMC by 2-fold, PC1 does not cleave the Lys-Lys or Arg-Lys bonds cleaved upon overexpression of PC2.
Similar articles
-
Role of prohormone convertases in pro-neuropeptide Y processing: coexpression and in vitro kinetic investigations.Biochemistry. 1997 Dec 23;36(51):16309-20. doi: 10.1021/bi9714767. Biochemistry. 1997. PMID: 9405066
-
Peptide biosynthetic processing: distinguishing prohormone convertases PC1 and PC2.Mol Cell Endocrinol. 1996 Jul 1;120(2):161-8. doi: 10.1016/0303-7207(96)03834-8. Mol Cell Endocrinol. 1996. PMID: 8832576
-
Post-translational processing of proopiomelanocortin (POMC) in mouse pituitary melanotroph tumors induced by a POMC-simian virus 40 large T antigen transgene.J Biol Chem. 1993 Nov 25;268(33):24967-75. J Biol Chem. 1993. PMID: 8227058
-
The subtilisin/kexin family of precursor convertases. Emphasis on PC1, PC2/7B2, POMC and the novel enzyme SKI-1.Ann N Y Acad Sci. 1999 Oct 20;885:57-74. doi: 10.1111/j.1749-6632.1999.tb08665.x. Ann N Y Acad Sci. 1999. PMID: 10816641 Review.
-
The cell biology of the prohormone convertases PC1 and PC2.Prog Nucleic Acid Res Mol Biol. 1999;63:69-108. doi: 10.1016/s0079-6603(08)60720-5. Prog Nucleic Acid Res Mol Biol. 1999. PMID: 10506829 Review.
Cited by
-
Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System.Front Pediatr. 2018 Jan 23;5:294. doi: 10.3389/fped.2017.00294. eCollection 2017. Front Pediatr. 2018. PMID: 29410949 Free PMC article. Review.
-
microRNA-Seq reveals cocaine-regulated expression of striatal microRNAs.RNA. 2011 Aug;17(8):1529-43. doi: 10.1261/rna.2775511. Epub 2011 Jun 27. RNA. 2011. PMID: 21708909 Free PMC article.
-
Modulation of PC1/3 activity by self-interaction and substrate binding.Endocrinology. 2011 Apr;152(4):1402-11. doi: 10.1210/en.2010-1170. Epub 2011 Feb 8. Endocrinology. 2011. PMID: 21303942 Free PMC article.
-
Mechanism of the facilitation of PC2 maturation by 7B2: involvement in ProPC2 transport and activation but not folding.J Cell Biol. 1997 Nov 3;139(3):625-38. doi: 10.1083/jcb.139.3.625. J Cell Biol. 1997. PMID: 9348280 Free PMC article.
-
Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis.J Neurochem. 2010 Mar;112(5):1168-79. doi: 10.1111/j.1471-4159.2009.06530.x. Epub 2009 Dec 7. J Neurochem. 2010. PMID: 19968759 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
