Proteolytic activation of single-chain precursor macrophage-stimulating protein by nerve growth factor-γ and epidermal growth factor-binding protein, members of the kallikrein family

Ming Hai Wang, Steven L. Gonias, Alison Skeel, Beni B. Wolf, Teizo Yoshimura, Edward J. Leonard

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Promacrophage-stimulating protein (MSP) is an 80-kDa protein that acquires biological activity after cleavage at an Arg-Val bond to a disulfide-linked αβ heterodimer by serine proteases of the intrinsic coagulation cascade. These proteases, which include serum kallikrein, factor XIIa and factor XIa, are members of the trypsin family of serine proteases. We now report that two other members of the family, nerve growth factor-γ (NGF-γ) and epidermal growth factor-binding protein (EGF-BP), cleave and activate pro-MSP to the disulfide-linked αβ heterodimer. Cleavage of 1.5 nM pro-MSP by 1 nM NGF-γ or EGF-BP at 37 °C was almost complete within 30 min. These concentrations of enzyme are about 2 orders of magnitude less than is required for cleavage by serum kallikrein or factor XIIa. Cleavage of pro-MSP to MSP was associated with a conformational change in the protein, because the cleaved product, but not pro-MSP, was detected by a sandwich enzyme-linked immunoassay. Cleavage caused the appearance of biological activity, as measured by chemotactic activity of MSP for resident peritoneal macrophages, by MSP-induced macrophage shape change, and by stimulation of macrophage ingestion of C3bi- coated erythrocytes. These findings suggest the possibility of cooperative interactions between NGF-γ or EGF-BP and pro-MSP in inflammation and wound healing.

Original languageEnglish
Pages (from-to)13806-13810
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number19
Publication statusPublished - May 13 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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