Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones
-
V. Hook
Abstract
Peptide neurotransmitters and hormones are synthesized as protein precursors that require proteolytic processing to generate smaller, biologically active peptides that are secreted to mediate neurotransmission and hormone actions. Neuropeptides within their precursors are typically flanked by pairs of basic residues, as well as by monobasic residues. In this review, evidence for secretory vesicle cathepsin L and Arg/Lys aminopeptidase as a distinct proteolytic pathway for processing the prohormone proenkephalin is presented. Cleavage of prohormone processing sites by secretory vesicle cathepsin L occurs at the NH[2]-terminal side of dibasic residues, as well as between the dibasic residues, resulting in peptide intermediates with Arg or Lys extensions at their NH[2]-termini. A subsequent Arg/Lys aminopeptidase step is then required to remove NH[2-]terminal basic residues to generate the final enkephalin neuropeptide. The cathepsin L and Arg/Lys aminopeptidase prohormone processing pathway is distinct from the proteolytic pathway mediated by the subtilisinlike prohormone convertases 1/3 and 2 (PC1/3 and PC2) with carboxypeptidase E/H. Differences in specific cleavage sites at paired basic residue sites distinguish these two pathways. These two proteolytic pathways demonstrate the increasing complexity of regulatory mechanisms for the production of peptide neurotransmitters and hormones.
Copyright © 2004 by Walter de Gruyter GmbH & Co. KG
Artikel in diesem Heft
- Highlight: 3rd General IPS Meeting/International Conference on Protease inhibitors
- Colon cancer: genomics and apoptotic events
- Interaction of calpastatin with calpain: a review
- Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones
- Searching for the most effective screening system to identify cell-active inhibitors of β-secretase
- Accumulation of mini-plasmin in the cerebral capillaries causes vascular invasion of the murine brain by a pneumotropic influenza A virus: implications for influenza-associated encephalopathy
- Protease degradomics: mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors
- Human cathepsin F: expression in baculovirus system, characterization and inhibition by protein inhibitors
- Proteinases participating in the processing and activation of prolegumain in primary cultured rat macrophages
- Human kallikrein 6 activity is regulated via an autoproteolytic mechanism of activation/inactivation
- Growth phase-dependent production of a cell wall-associated elastinolytic cysteine proteinase by Staphylococcus epidermidis
- Evidence for an interaction between leptin, T cell costimulatory antigens CD28, CTLA-4 and CD26 (dipeptidyl peptidase IV) in BCG-induced immune responses of leptin- and leptin receptor-deficient mice
- Characterisation of a highly specific, endogenous inhibitor of cysteine protease from Staphylococcus epidermidis, a new member of the staphostatin family
- Identification of cysteine protease inhibitors that belong to cystatin family 1 in the cellular slime mold Dictyostelium discoideum
- High molecular weight kininogen as substrate for cathepsin B
- 'Dipeptidyl peptidase-IV activity and/or structure homologs' (DASH) in growth-modulated glioma cell lines
- The crystal structure of human dipeptidyl peptidase IV (DPPIV) complex with diprotin A
- Metalloproteases with EGF, CUB, and thrombospondin-1 domains function in molting of Caenorhabditis elegans
Artikel in diesem Heft
- Highlight: 3rd General IPS Meeting/International Conference on Protease inhibitors
- Colon cancer: genomics and apoptotic events
- Interaction of calpastatin with calpain: a review
- Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones
- Searching for the most effective screening system to identify cell-active inhibitors of β-secretase
- Accumulation of mini-plasmin in the cerebral capillaries causes vascular invasion of the murine brain by a pneumotropic influenza A virus: implications for influenza-associated encephalopathy
- Protease degradomics: mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors
- Human cathepsin F: expression in baculovirus system, characterization and inhibition by protein inhibitors
- Proteinases participating in the processing and activation of prolegumain in primary cultured rat macrophages
- Human kallikrein 6 activity is regulated via an autoproteolytic mechanism of activation/inactivation
- Growth phase-dependent production of a cell wall-associated elastinolytic cysteine proteinase by Staphylococcus epidermidis
- Evidence for an interaction between leptin, T cell costimulatory antigens CD28, CTLA-4 and CD26 (dipeptidyl peptidase IV) in BCG-induced immune responses of leptin- and leptin receptor-deficient mice
- Characterisation of a highly specific, endogenous inhibitor of cysteine protease from Staphylococcus epidermidis, a new member of the staphostatin family
- Identification of cysteine protease inhibitors that belong to cystatin family 1 in the cellular slime mold Dictyostelium discoideum
- High molecular weight kininogen as substrate for cathepsin B
- 'Dipeptidyl peptidase-IV activity and/or structure homologs' (DASH) in growth-modulated glioma cell lines
- The crystal structure of human dipeptidyl peptidase IV (DPPIV) complex with diprotin A
- Metalloproteases with EGF, CUB, and thrombospondin-1 domains function in molting of Caenorhabditis elegans
