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

Lloyd D. Fricker, Audra A. McKinzie, Jilin Sun, Eileen Curran, Yimei Qian, Lin Yan, Scott D. Patterson, Paul L. Courchesne, Bill Richards, Nancy Levin, Nino Mzhavia, Lakshmi A. Devi, James Douglass

Research output: Contribution to journalArticle

184 Citations (Scopus)

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 IC50 of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

Original languageEnglish (US)
Pages (from-to)639-648
Number of pages10
JournalJournal of Neuroscience
Volume20
Issue number2
StatePublished - Jan 15 2000

Fingerprint

Chromogranins
Proprotein Convertase 1
Peptides
Brain
Proprotein Convertase 2
Carboxypeptidase H
Pro-Opiomelanocortin
Messenger RNA
Neuropeptides
Inhibitory Concentration 50
Pancreas
Neurons
Enzymes

Keywords

  • 7B2
  • Carboxypeptidase E
  • Chromogranin
  • Neuropeptide
  • Prohormone convertase
  • Secretogranin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

In: Journal of Neuroscience, Vol. 20, No. 2, 15.01.2000, p. 639-648.

Research output: Contribution to journalArticle

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 2000, 'Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing', Journal of Neuroscience, vol. 20, no. 2, pp. 639-648.
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. / Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 2. pp. 639-648.
@article{a4d889d083c6426d8c040102553285fd,
title = "Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing",
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 IC50 of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.",
keywords = "7B2, Carboxypeptidase E, Chromogranin, Neuropeptide, Prohormone convertase, Secretogranin",
author = "Fricker, {Lloyd D.} and McKinzie, {Audra A.} and Jilin Sun and Eileen Curran and Yimei Qian and Lin Yan and Patterson, {Scott D.} and Courchesne, {Paul L.} and Bill Richards and Nancy Levin and Nino Mzhavia and Devi, {Lakshmi A.} and James Douglass",
year = "2000",
month = "1",
day = "15",
language = "English (US)",
volume = "20",
pages = "639--648",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "2",

}

TY - JOUR

T1 - Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing

AU - Fricker, Lloyd D.

AU - McKinzie, Audra A.

AU - Sun, Jilin

AU - Curran, Eileen

AU - Qian, Yimei

AU - Yan, Lin

AU - Patterson, Scott D.

AU - Courchesne, Paul L.

AU - Richards, Bill

AU - Levin, Nancy

AU - Mzhavia, Nino

AU - Devi, Lakshmi A.

AU - Douglass, James

PY - 2000/1/15

Y1 - 2000/1/15

N2 - 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 IC50 of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

AB - 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 IC50 of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

KW - 7B2

KW - Carboxypeptidase E

KW - Chromogranin

KW - Neuropeptide

KW - Prohormone convertase

KW - Secretogranin

UR - http://www.scopus.com/inward/record.url?scp=0034651077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034651077&partnerID=8YFLogxK

M3 - Article

C2 - 10632593

AN - SCOPUS:0034651077

VL - 20

SP - 639

EP - 648

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 2

ER -