Evidence for distinct dibasic processing endopeptidases with Lys-Arg and Arg-Arg specificities in neurohypophysial secretory granules. 1992

Y Rouille, and A Spang, and J Chauvet, and R Acher
Laboratory of Biological Chemistry, University of Paris VI, France.

Two Ca(2+)-dependent endopeptidases endowed with specificities for paired basic residues have been disclosed in rat and ox neurohypophysial secretory granules. Specificities investigated by using synthetic fluorogenic substrates showed the presence of a Lys-Arg endopeptidase with optimum pH close to the granule pH (5.5) and of an Arg-Arg endopeptidase more active at pH 7.0. Granule extracts have virtually no activity towards Lys-Lys-containing substrate or monobasic substrates. Pro-Gly-Lys-Arg-chloromethylketone appears a very efficient inhibitor for the Lys-Arg enzyme. Soluble and membrane-bound forms of both endopeptidases have been detected. pH-dependence of membrane binding and partitioning into Triton X-114 suggest that the membrane-bound form of Lys-Arg endopeptidase is associated through an amphiphilic alpha-helix. It is proposed that the enzyme Lys-Arg cleaves prooxytocin and provasopressin at their signal sequence Gly-Lys-Arg when these precursors arrive in the neurosecretory granules. The processing proceeds in the granules through carboxypeptidase E and alpha-amidating enzyme complex for giving mature pharmacologically active nonapeptide hormones.

UI MeSH Term Description Entries
D009481 Neurophysins Carrier proteins for OXYTOCIN and VASOPRESSIN. They are polypeptides of about 10-kDa, synthesized in the HYPOTHALAMUS. Neurophysin I is associated with oxytocin and neurophysin II is associated with vasopressin in their respective precursors and during transportation down the axons to the neurohypophysis (PITUITARY GLAND, POSTERIOR). Neurophysin,Neurophysin I,Neurophysin II,Neurophysin III,Oxytocin-Associated Neurophysin,Vasopressin-Associated Neurophysin,Neurophysin, Oxytocin-Associated,Neurophysin, Vasopressin-Associated,Oxytocin Associated Neurophysin,Vasopressin Associated Neurophysin
D010121 Oxytocin A nonapeptide hormone released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). It differs from VASOPRESSIN by two amino acids at residues 3 and 8. Oxytocin acts on SMOOTH MUSCLE CELLS, such as causing UTERINE CONTRACTIONS and MILK EJECTION. Ocytocin,Pitocin,Syntocinon
D010450 Endopeptidases A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS. Endopeptidase,Peptide Peptidohydrolases
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D010904 Pituitary Gland, Posterior Neural tissue of the pituitary gland, also known as the neurohypophysis. It consists of the distal AXONS of neurons that produce VASOPRESSIN and OXYTOCIN in the SUPRAOPTIC NUCLEUS and the PARAVENTRICULAR NUCLEUS. These axons travel down through the MEDIAN EMINENCE, the hypothalamic infundibulum of the PITUITARY STALK, to the posterior lobe of the pituitary gland. Neurohypophysis,Infundibular Process,Lobus Nervosus,Neural Lobe,Pars Nervosa of Pituitary,Posterior Lobe of Pituitary,Gland, Posterior Pituitary,Infundibular Processes,Lobe, Neural,Lobes, Neural,Nervosus, Lobus,Neural Lobes,Pituitary Pars Nervosa,Pituitary Posterior Lobe,Posterior Pituitary Gland,Posterior Pituitary Glands,Process, Infundibular,Processes, Infundibular
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D011498 Protein Precursors Precursors, Protein
D011499 Protein Processing, Post-Translational Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility. Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003594 Cytoplasmic Granules Condensed areas of cellular material that may be bounded by a membrane. Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic

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