Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Messenger RNA extracted from rat medullary carcinoma of the thyroid directs the synthesis in cell-free translation systems of a precursor of calcitonin, Mr = 15,000, substantially larger than the mature form of the hormone, Mr = 3,500. When translations of the mRNA were carried out in the presence of microsomal membranes prepared from a canine pancreas, a larger product (apparent Mr = 17,000) was observed by electrophoresis of the labeled proteins in the translation mixtures on sodium dodecyl sulfate-polyacrylamide gels. This membrane-processed product of Mr = 17,000 was specifically immunoprecipitated by an antiserum to synthetic calcitonin and bound to concanavalin A-Sepharose. Incubation of the proteins synthesized in the cell-free translations performed in the presence of microsomal membranes with the glycosidase, endo-beta-N-acetylglucosaminidase H, reduced the apparent molecular weight of the membrane-processed precursor from 17,000 to 12,000. In addition, the processed Mr = 17,000 calcitonin-related precursor, but not the initial, unprocessed precursor of Mr = 15,000, was resistant to proteolytic digestion by a mixture of trypsin and chymotrypsin. These results indicate that the biosynthesis of calcitonin involves the glycosylation and proteolytic cleavage of a newly synthesized precursor along with sequestration of the processed precursor within microsomal vesicles. Thus, the calcitonin precursor undergoes extensive co- and post-translational processing to the smaller, unglycosylated hormone that is secreted.
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PMID:Procalcitonin is a glycoprotein. 720 75

Neurotensin (NT) and neuromedin N (NN) are two related biologically active peptides that are encoded in the same precursor molecule. In the rat, the precursor consists of a 169-residue polypeptide starting with an N-terminal signal peptide and containing in its C-terminal region one copy each of NT and NN. NN precedes NT and is separated from it by a Lys-Arg sequence. Two other Lys-Arg sequences flank the N-terminus of NN and the C-terminus of NT. A fourth Lys-Arg sequence occurs near the middle of the precursor and is followed by an NN-like sequence. Finally, an Arg-Arg pair is present within the NT moiety. The four Lys-Arg doublets represent putative processing sites in the precursor molecule. The present study was designed to investigate the post-translational processing of the NT/NN precursor in the rat medullary thyroid carcinoma (rMTC) 6-23 cell line, which synthesizes large amounts of NT upon dexamethasone treatment. Five region-specific antisera recognizing the free N- or C-termini of sequences adjacent to the basic doublets were produced, characterized and used for immunoblotting and radioimmunoassay studies in combination with gel filtration, reverse-phase h.p.l.c. and trypsin digestion of rMTC 6-23 cell extracts. Because two of the antigenic sequences, i.e. NN and the NN-like sequence, start with a lysine residue that is essential for recognition by their respective antisera, a micromethod by which trypsin specifically cleaves at arginine residues was developed. The results show that dexamethasone-treated rMTC 6-23 cells produced comparable amounts of NT, NN and a peptide corresponding to a large N-terminal precursor fragment lacking the NN and NT moieties. This large fragment was purified. N-Terminal sequencing revealed that it started at residue Ser23 of the prepro-NT/NN sequence, and thus established the Cys22-Ser23 bond as the cleavage site of the signal peptide. Two other large N-terminal fragments bearing respectively the NN and NT sequences at their C-termini were present in lower amounts. The NN-like sequence was internal to all the large fragments. There was no evidence for the presence of peptides with the NN-like sequence at their N-termini. This shows that, in rMTC 6-23 cells, the precursor is readily processed at the three Lys-Arg doublets that flank and separate the NT and NN sequences. In contrast, the Lys-Arg doublet that precedes the NN-like sequence is not processed in this system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunological and biochemical characterization of processing products from the neurotensin/neuromedin N precursor in the rat medullary thyroid carcinoma 6-23 cell line. 847 Oct 39

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard tumor marker calcitonin, plasma carcino-embryonic antigen (CEA), plasma catecholamines, (platelet) serotonin, chromogranin A, tryptase, and urinary markers of catecholamine, histamine, and serotonin metabolism were prospectively determined in 46 patients with histologically proven MTC. Patients were divided according to the stage of disease: group 1, no evidence; group 2, stable disease (SD); and group 3, progressive disease (PD). Plasma dopamine was increased in the majority of the patients with SD and PD; however it did not correlate with extent of disease. Elevated plasma platelet levels of serotonin were only present in patients with multiple endocrine neoplasia 2 with SD or PD but did not differ between those groups. Histamine metabolites were elevated in 20% of patients with SD and PD. In addition to plasma calcitonin, only CEA and chromogranin A could differentiate between stable and progressive MTC. MTCs are capable of synthesizing catecholamines, serotonin, and histamine metabolites underscoring that MTCs have metabolic characteristics in common with other neuroendocrine tumors. Thus far, clinical usefulness and relevance seems limited. The most useful markers in the follow-up of MTC are plasma calcitonin and CEA.
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PMID:Biochemical markers in the follow-up of medullary thyroid cancer. 1712 44