Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor

Gregg Joslin, James E. Krause, Andrew D. Hershey, Steven P. Adams, Robert Fallon, David H. Perlmutter

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

During the formation of an inhibitory complex with neutrophil elastase, α1 antitrypsin (α1 AT) undergoes a structural rearrangement and the resulting α1 AT-elastase complex becomes endowed with chemoattractant activities, mediates an increase in synthesis of α1 AT, and is rapidly cleared from the circulation. In previous studies we have provided evidence that these biological activities involve the recognition of a conformation-specific domain in the α1 AT molecule by a cell surface receptor on human hepatoma HepG2 cells and human monocytes. The receptor has been termed the serpin-enzyme complex (SEC) receptor because it also recognizes complexes of serpins antithrombin III, α1 anti-chymotrypsin, and C1 inhibitor with their cognate enzymes. Because a pentapeptide domain of α1 AT (amino acids 370-374, Phe-Val-Phe-Leu-Met) is sufficient for binding to the SEC receptor and the sequence of this domain is remarkably similar to those of substance P, several other tachykinins, bombesin, and the amyloid-β peptide, we have examined the possibility that these other ligands bind to the SEC receptor. The results indicate that substance P, several other tachykinins, and bombesin compete for binding to, and cross-linking of, the SEC receptor. The SEC receptor is distinct from the substance P receptor by several criteria. There is no substance P receptor mRNA in HepG2 cells; the SEC receptor is present in much higher density on receptor-bearing cells and binds its ligands at lower affinity than the substance P receptor; the SEC receptor is much less restricted in the specificity with which it recognizes ligand; ligands for the SEC receptor including peptide 105Y (based on α1AT sequence 359-374), α1 AT-protease complexes, and bombesin do not compete for binding of substance P to a stable transfected cell line expressing the substance P receptor. Finally, we show here that the amyloid-β peptide competes for binding to the SEC receptor but does not bind to the substance P receptor, therein raising the possibility that the SEC receptor is involved in certain biological activities, including the recently described neurotrophic and neurotoxic effects ascribed to the amyloid-β peptide.

Original languageEnglish (US)
Pages (from-to)21897-21902
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number32
StatePublished - 1991
Externally publishedYes

Fingerprint

Bombesin
Substance P
Amyloid
Neurokinin-1 Receptors
Peptides
Ligands
Tachykinins
Hep G2 Cells
Bioactivity
Bearings (structural)
serpin-enzyme complex receptor
peptide P
Serpins
Leukocyte Elastase
Antithrombin III
Pancreatic Elastase
Chemotactic Factors
Chymotrypsin
Cell Surface Receptors
Conformations

ASJC Scopus subject areas

  • Biochemistry

Cite this

Joslin, G., Krause, J. E., Hershey, A. D., Adams, S. P., Fallon, R., & Perlmutter, D. H. (1991). Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor. Journal of Biological Chemistry, 266(32), 21897-21902.

Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor. / Joslin, Gregg; Krause, James E.; Hershey, Andrew D.; Adams, Steven P.; Fallon, Robert; Perlmutter, David H.

In: Journal of Biological Chemistry, Vol. 266, No. 32, 1991, p. 21897-21902.

Research output: Contribution to journalArticle

Joslin, G, Krause, JE, Hershey, AD, Adams, SP, Fallon, R & Perlmutter, DH 1991, 'Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor', Journal of Biological Chemistry, vol. 266, no. 32, pp. 21897-21902.
Joslin G, Krause JE, Hershey AD, Adams SP, Fallon R, Perlmutter DH. Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor. Journal of Biological Chemistry. 1991;266(32):21897-21902.
Joslin, Gregg ; Krause, James E. ; Hershey, Andrew D. ; Adams, Steven P. ; Fallon, Robert ; Perlmutter, David H. / Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 32. pp. 21897-21902.
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