Keywords:
Protein precursors.
;
Peptide hormones.
;
Electronic books.
Description / Table of Contents:
The prohormone convertases (PC) 1/3 and 2 are calcium-activated eukaryotic subtilisins with low pH optima which accomplish the limited proteolysis of peptide hormone precursors within neurons and endocrine cells. In this lecture, we review the biochemistry, regulation, and roles of PC1/3 and 2 in disease, with an emphasis on the work published in the last 10 years. In the 20 years since their discovery, a great deal has been learned about their localization and cellular functions. Both PCs share the same four domains: the propeptides perform important roles in controlling activation and targeting; the catalytic domains confer specificity, with PC1/3 possessing a more restricted binding pocket than that of PC2; the P domain is required for expression and contributes to enzymatic properties; and the C-terminal tail assists in proper routing to granules. PC1/3, but not PC2, exists in full-length and C-terminally truncated forms that exhibit different biochemical properties. Both enzymes associate with binding proteins; proSAAS is thought to modulate precursor cleavage by PC1/3, while co-expression of 7B2 is obligatory for the formation of active PC2. Finally, new studies have revealed an increasingly important role for PC1/3 polymorphisms and mutations in glucose homeostasis and obesity. Table of Contents: General Introduction to the Prohormone Convertases / Prohormone Convertase 1/3 / Prohormone Convertase 2 / Summary and Future Directions / References / Author Biography.
Type of Medium:
Online Resource
Pages:
1 online resource (114 pages)
Edition:
1st ed.
ISBN:
9781615043651
Series Statement:
Colloquium Series on Neuropeptides Series
URL:
https://ebookcentral.proquest.com/lib/geomar/detail.action?docID=881346
DDC:
612.822
Language:
English
Note:
Intro -- Peptide Biosynthesis: Prohormone Convertases 1/3 and 2 -- Colloquium Series on Neuropeptides -- Abstract -- Keywords -- Contents -- chapter 1: General Introduction to the Prohormone Convertases -- chapter 2: Prohormone Convertase 1/3 -- 2.1 Introduction to Prohormone Convertase 1/3 -- 2.1.1 Unique Features -- 2.1.2 Evolution -- 2.1.3 Domain Structure -- 2.1.4 PC1/3 Binding Protein: proSAAS -- 2.1.5 Gene Location -- 2.2 Distribution -- 2.2.1 Tissue Distribution -- 2.2.2 Intracellular Distribution -- 2.2.3 Cell Lines -- 2.2.4 Development -- 2.3 Cell Biology and Maturation -- 2.3.1 PC1/3 Maturation and Posttranslational Modifications -- 2.3.2 Targeting of PC1/3 -- 2.4 Enzymatic Characterization -- 2.4.1 General Enzymatic Properties -- 2.4.2 Contribution of Various Domains to Enzymatic Properties -- 2.4.3 Substrate Specificity -- 2.5 Regulation of Expression and Activity -- 2.5.1 Transcriptional and Translational Control -- 2.5.2 Endogenous Regulators -- 2.5.3 Regulation of PC1/3 Activity by its Chaperone proSAAS -- 2.5.4 Synthetic Inhibitors and Activators -- 2.6 Model Systems, Knockouts and Mutants -- 2.6.1 PC1/3 Knockout Mice -- 2.6.2 PC1/3 Asn222Asp Mutant Mouse -- 2.6.3 proSAAS Transgenic and Knockout Mice -- 2.7 PC1/3 as a Therapeutic Target -- 2.7.1 Human Mutations -- 2.7.2 Single Nucleotide Polymorphisms (SNPs) -- 2.7.3 PC1/3 and Other Diseases -- 2.7.4 ProSAAS and Disease Relevance -- chapter 3: Prohormone Convertase 2 -- 3.1 Introduction to Prohormone Convertase 2 -- 3.1.1 Unique Features -- 3.1.2 Evolution -- 3.1.3 Domain Structure and Functions -- 3.1.4 The PC2-Binding Protein 7B2 -- 3.1.5 Gene Location -- 3.2 Distribution -- 3.2.1 Tissue Distribution -- 3.2.2 Intracellular Distribution -- 3.2.3 Cell Lines -- 3.2.4 Development -- 3.3 Cell Biology and Maturation -- 3.3.1 ProPC2 Maturation -- 3.3.2 7B2 and proPC2/PC2 Targeting.
,
3.4 Enzymatic Characterization -- 3.4.1 General Enzymatic Properties -- 3.4.2 Contribution of Various Domains to Enzymatic Activity -- 3.4.3 Tissue Analysis of PC2 Activity -- 3.4.4 Substrate Specificity -- 3.5 Regulation of Expression and Activity -- 3.5.1 Transcriptional and Translational Regulation -- 3.5.2 Endogenous Inhibitors -- 3.5.3 Synthetic Inhibitors and Activators -- 3.5.4 Regulation of PC2 Activity by its Chaperone 7B2 -- 3.5.5 Regulation of 7B2 Expression -- 3.6 Model Systems, Knockouts, and Mutants -- 3.6.1 The PC2 Knockout -- 3.6.2 The 7B2 Knockout -- 3.6.3 Model Systems -- 3.7 PC2 as a Therapeutic Target: Disease Relevance -- 3.7.1 Polymorphisms -- 3.7.2 Cancer -- chapter 4: Summary and Future Directions -- References -- Author Biographies.
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