Disease relevance of CPZ

• In luteinizing hormone/follicle-stimulating hormone (LH/FSH)-producing gonadotroph adenomas, which do not require carboxypeptidases to produce gonadotropins, only CPZ immunostaining was demonstrated [1].
• This study evaluated the expression patterns of CPE, CPD, and CPZ immunoreactivity in 48 pituitary adenomas [1].
• The 641-amino acid form of CPZ expressed in the baculovirus system cleaves 5-dimethylaminonaphthalene-1-sulfonyl (dansyl)-Phe-Ala-Arg, although the level of enzyme activity was approximately 10-fold lower than either carboxypeptidase E or D expressed using the same viral system [2].
• A human adenocarcinoma of the colon shows expression of CPZ in the extracellular matrix adjacent to malignant cells [3].
• Endogenous CPZ in the PC12 rat pheochromocytoma cell line is also associated with the extracellular matrix [3].

High impact information on CPZ

• Carboxypeptidase Z (CPZ) is a newly reported member of the metallocarboxypeptidase gene family, but unlike other members of this family, CPZ contains an N-terminal domain that has amino acid sequence similarity to Wnt-binding proteins [3].
• CPZ is also present in amnion cells, but is not readily apparent in the extracellular matrix of this cell type [3].
• In human placenta, CPZ is present within invasive trophoblasts and in the surrounding extracellular space, indicating an association with extracellular matrix [3].
• Carboxypeptidase Z is present in the regulated secretory pathway and extracellular matrix in cultured cells and in human tissues [3].

Biological context of CPZ

• The major form of CPZ mRNA in human salivary gland encodes a protein with an open reading frame of 641 amino acids [2].
• However, CPZ differs from the other enzymes in that CPZ is enriched in the extracellular matrix and is broadly distributed during early embryogenesis [4].

Anatomical context of CPZ

• In null-cell adenomas, CPE immunoreactivity was detected in the majority of tumors, but CPD and CPZ were identified only in a minority of cases [1].
• When expressed in the AtT-20 mouse pituitary cell line, CPZ protein is routed to the regulated secretory pathway and secreted upon stimulation [3].
• Mild to moderate immunoreactivities for CPE and CPZ were distributed relatively uniformly in the majority of the anterior pituitary cells and basophil invasion [5].
• Northern blot analysis showed rat CPZ mRNA to be abundant in the placenta, with low to moderate levels in the brain, lung, thymus, and kidney [6].
• The BRL3A rat liver cell line and the PC12 rat adrenal cell line express high levels of CPZ mRNA [6].

Associations of CPZ with chemical compounds

• In addition to containing a metallocarboxypeptidase domain, CPZ also contains a Cys-rich domain that has homology to Wnt-binding proteins; Wnts are important signaling molecules during development [4].

Physical interactions of CPZ

• CPZ binds myristoylated as well as non-myristoylated NCS-1 in Ca(2+)-dependent manner, with dynamic interaction to myristoylated protein [7].

Other interactions of CPZ

• However, the distribution of CPZ and AEBP1 differ in pituitary and thyroid [6].
• Carboxypeptidase Z is a serine carboxypeptidase secreted by Absidia zychae NRIC 1199 [8].

Analytical, diagnostic and therapeutic context of CPZ

• In order to gain insights as to the potential function of CPZ, the intracellular localization of this protein was determined in cell culture and in human tissues [3].
• In situ hybridization analysis indicated that CPZ is expressed only in specific cell types [6].
• Sequence analysis showed rat and human CPZ to be highly conserved within the frizzled domain (77% amino acid identity), the carboxypeptidase domain (91%), and the C-terminal 28 residues (78%) [6].
• Early subjective response and symptom change at twenty-four and forty-eight hours following initiation of drug therapy with either CPZ or haloperidol were the only variables that significantly related to therapeutic outcome [9].
• Increase in activity for the C-terminal Pro-X bond by site-directed mutagenesis of Gly137 to Ala in carboxypeptidase Z [10].

References