Identification and Characterization of proSAAS, a Granin-Like Neuroendocrine Peptide Precursor that Inhibits Prohormone Processing

Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroe...

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Bibliographic Details
Published in:The Journal of neuroscience 2000-01, Vol.20 (2), p.639-648
Main Authors: Fricker, Lloyd D, McKinzie, Audra A, Sun, Jilin, Curran, Eileen, Qian, Yimei, Yan, Lin, Patterson, Scott D, Courchesne, Paul L, Richards, Bill, Levin, Nancy, Mzhavia, Nino, Devi, Lakshmi A, Douglass, James
Format: Article
Language:English
Subjects:
Adrenal Glands - metabolism
Amino Acid Sequence
Animals
Base Sequence
Brain - metabolism
carboxypeptidase E
Carboxypeptidase H
Carboxypeptidases - deficiency
Carboxypeptidases - genetics
Carboxypeptidases - metabolism
Cell Line
Humans
Kinetics
Mice
Mice, Mutant Strains
Molecular Sequence Data
Neurons - metabolism
Neuropeptides - biosynthesis
Neuropeptides - chemistry
Neuropeptides - genetics
Neuropeptides - metabolism
Organ Specificity
Pancreas - metabolism
Pituitary Gland - metabolism
Pro-Opiomelanocortin - genetics
Pro-Opiomelanocortin - metabolism
prohormone convertase
Protein Precursors - chemistry
Protein Precursors - genetics
Protein Precursors - metabolism
Protein Processing, Post-Translational
Rats
Recombinant Proteins - metabolism
RNA, Messenger - genetics
Sequence Alignment
Sequence Homology, Amino Acid
Transfection
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Summary:Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.20-02-00639.2000