Carboxypeptidase B-like converting enzyme activity in secretory granules of rat pituitary.

Abstract

Recent amino acid sequence data suggest that trypsin-like and carboxypeptidase B-like activities are required for the processing of pituitary prohormones-e.g., pro-opiocortin (pro-adrenocorticotropin/lipotropin) and provasopressin in secretory granules. In this study the existence of a carboxypeptidase B activity in purified secretory granules from anterior, intermediate, and neural lobes of rat pituitary has been examined. A carboxypeptidase B activity that cleaved the COOH-terminal -Lys-Lys-Arg residues from the adrenocorticotropin fragment ACTH-(1-17) (a potential hormone product liberated from pro-opiocortin by a trypsin-like enzyme) was detected in anterior and intermediate lobe granules. A similar carboxypeptidase B activity was also present in purified secretory granules from rat pituitary neural lobes that The carboxypeptidase B in secretory granules from all three lobes was shown to be active at pH 5.5, but not at pH 7.4. Inhibition by the zinc metallocarboxypeptidase inhibitors guanidinopropylsuccinic acid, aminomercaptosuccinic acid, benzylsuccinic acid, 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, and the potato carboxypeptidase B inhibitor, and inhibition by the metal chelators EDTA and 1,10-phenanthroline demonstrate metal ion dependence of the pituitary granule carboxypeptidase activities. However, Co2+ stimulated the secretory granule carboxypeptidase B activities. Thiol protease inhibitors such as Cu + and p-chloromercuriphenylsulfonic acid also inhibited the activity. Thus, the secretory granule carboxypeptidase B-like activities in all three lobes of the pituitary appear to be similar thiol-metallopeptidases that differ from other carboxypeptidase activities previously described and may play an exclusive role in hormone biosynthesis in the pituitary.

An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers

“…Elucidating and studying new molecules that drive tumor metastasis could lead to a better understanding of the mechanisms underlying this complex process (4,5) and also provide potential prognostic markers and therapeutic targets for clinical use. In the present study we show, for the first time to our knowledge, that a splice isoform of the prohormone processing enzyme carboxypeptidase E (CPE) (6,7), CPE-ΔN, induces tumor growth and metastasis and is a powerful biomarker for predicting future development of extra-and intrahepatic metastasis (recurrence) in patients with hepatocel-lular carcinoma (HCC; as an epithelial cell-derived tumor) and pheochromocytoma/paraganglioma (PHEO/PGL; as a neuroendocrine cell-derived tumor).…”

A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons

“…Carboxypeptidase E (CPE) is a proneuropeptide/prohormone processing enzyme (Fricker and Snyder, 1982;Hook and Loh, 1984) and is associated with BDNF vesicles in hippocampal and cortical neurons (Lou et al, 2005). The luminal domain of the membrane form of CPE acts as a sorting receptor for targeting BDNF to the regulated secretory pathway vesicles in hippocampal and cortical neurons (Lou et al 2005).…”

视网膜神经节细胞-5应激损伤后原蛋白转化酶-2和羧基肽酶-E介导的神经肽加工

“…Tanaka S et al [12] reported that proPC2 with 638 amino acid residues (74 kDa) is activated into mature PC2 with 529 amino acid residues (64 kDa) in adequate conditions, such as pH 5.0, other PCs and higher Ca 2+ . The soluble CPE (sCPE) is an exopeptidase that cleaves neuro-endocrinopeptides with C-terminal basic amino acids and produces active forms of peptide hormones and neuropeptides [13,14] . The membrane-bound CPE (mCPE) functions as a sorting receptor in the trans-Golgi network (TGN) and facilitates the sorting of pro-hormones into the regulated secretory pathway [15,16] .…”