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PMID: 10632593 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 2 ·2000-01-15 ·Pages 639-48

Fricker LD, McKinzie AA, Sun J, Curran E, Qian Y, Yan L, Patterson SD, Courchesne PL, Richards B, Levin N, Mzhavia N, Devi LA, Douglass J

Abstract

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.

MeSH Terms
Adrenal Glands/metabolism Amino Acid Sequence Animals Base Sequence Brain/metabolism Carboxypeptidase H Carboxypeptidases/deficiency,genetics,metabolism Cell Line Humans Kinetics Mice Mice, Mutant Strains Molecular Sequence Data Neurons/metabolism Neuropeptides/biosynthesis,chemistry,genetics,metabolism Organ Specificity Pancreas/metabolism Pituitary Gland/metabolism Pro-Opiomelanocortin/genetics,metabolism Protein Precursors/chemistry,genetics,metabolism Protein Processing, Post-Translational RNA, Messenger/genetics Rats Recombinant Proteins/metabolism Sequence Alignment Sequence Homology, Amino Acid Transfection
Chemicals
Neuropeptides PCSK1N protein, human Protein Precursors RNA, Messenger Recombinant Proteins Pro-Opiomelanocortin Carboxypeptidases Carboxypeptidase H
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Fricker L D
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. [email protected]
McKinzie A A
Sun J
Curran E
Qian Y
Yan L
Patterson S D
Courchesne P L
Richards B
Levin N
Mzhavia N
Devi L A
Douglass J
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
[email protected]
Published
2000-01-15
Pages
639-48
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772395
Subset
IM
Grants
NIDA NIH HHS · K02DA-00194 · United States
NIDA NIH HHS · R01DA04494 · United States
NINDS NIH HHS · R01NS-26880 · United States
External Links
PubMed source PMC Full Text View journal details
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