Document Detail


Proteolytic activation of single-chain precursor macrophage-stimulating protein by nerve growth factor-gamma and epidermal growth factor-binding protein, members of the kallikrein family.
MedLine Citation:
PMID:  8188657     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Promacrophage-stimulating protein (MSP) is an 80-kDa protein that acquires biological activity after cleavage at an Arg-Val bond to a disulfide-linked alpha beta 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-gamma (NGF-gamma) and epidermal growth factor-binding protein (EGF-BP), cleave and activate pro-MSP to the disulfide-linked alpha beta heterodimer. Cleavage of 1.5 nM pro-MSP by 1 nM NGF-gamma or EGF-BP at 37 degrees 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-gamma or EGF-BP and pro-MSP in inflammation and wound healing.
Authors:
M H Wang; S L Gonias; A Skeel; B B Wolf; T Yoshimura; E J Leonard
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  269     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1994 May 
Date Detail:
Created Date:  1994-06-22     Completed Date:  1994-06-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  13806-10     Citation Subset:  IM    
Affiliation:
Immunopathology Section, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cricetinae
Endopeptidases / metabolism*
Growth Substances / genetics,  metabolism*
Hepatocyte Growth Factor*
Humans
Hydrolysis
Kallikreins / genetics,  metabolism*
Nerve Growth Factors / metabolism*
Protein Precursors / genetics,  metabolism*
Proto-Oncogene Proteins*
Serine Endopeptidases / metabolism*
Chemical
Reg. No./Substance:
0/Growth Substances; 0/Nerve Growth Factors; 0/Protein Precursors; 0/Proto-Oncogene Proteins; 0/macrophage stimulating protein; 67256-21-7/Hepatocyte Growth Factor; EC 3.4.-/Endopeptidases; EC 3.4.21.-/Kallikreins; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/nerve growth factor, gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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