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

187 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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    Fricker, L. D., 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. (2000). Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. Journal of Neuroscience, 20(2), 639-648.