PMID- 10198291
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20161124
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 112 ( Pt 7)
DP  - 1999 Apr
TI  - Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by
      PACE/furin-like activity required for incorporation in the matrix.
PG  - 1093-100
AB  - Fibrillin-1, the main component of 10-12 nm microfibrils of the extracellular
      matrix, is synthesized as profibrillin and proteolytically processed to
      fibrillin. The putative cleavage site has been mapped to the carboxy-terminal
      domain of profibrillin-1, between amino acids arginine 2731 and serine 2732, by a
      spontaneous mutation in this recognition site that prevents profibrillin
      conversion. This site contains a basic amino acid recognition sequence
      (R-G-R-K-R-R) for proprotein convertases of the furin/PACE family. In this study,
      we use a mini-profibrillin protein to confirm the cleavage in the
      carboxy-terminal domain by both fibroblasts and recombinantly expressed
      furin/PACE, PACE4, PC1/3 and PC2. Site-directed mutagenesis of amino acids in the
      consensus recognition motif prevented conversion, thereby identifying the
      scissile bond and characterizing the basic amino acids required for cleavage.
      Using a PACE/furin inhibitor, we show that wild-type profibrillin is not
      incorporated into the extracellular matrix until it is converted to fibrillin.
      Therefore, profibrillin-1 is the first extracellular matrix protein to be shown
      to be a substrate for subtilisin-like proteases, and the conversion of
      profibrillin to fibrillin controls microfibrillogenesis through exclusion of
      uncleaved profibrillin.
FAU - Raghunath, M
AU  - Raghunath M
AD  - Department of Physiological Chemistry and Pathobiochemistry and of Medical
      Physics and Biophysics, University of Munster, Munster, Germany.
FAU - Putnam, E A
AU  - Putnam EA
FAU - Ritty, T
AU  - Ritty T
FAU - Hamstra, D
AU  - Hamstra D
FAU - Park, E S
AU  - Park ES
FAU - Tschodrich-Rotter, M
AU  - Tschodrich-Rotter M
FAU - Peters, R
AU  - Peters R
FAU - Rehemtulla, A
AU  - Rehemtulla A
FAU - Milewicz, D M
AU  - Milewicz DM
LA  - eng
GR  - R01 AR43626A/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (DNA Primers)
RN  - 0 (Fibrillins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Protein Precursors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 526U7A2651 (Egtazic Acid)
RN  - EC 3.4.21.- (Subtilisins)
RN  - EC 3.4.21.75 (Furin)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - DNA Primers
MH  - Dose-Response Relationship, Drug
MH  - Egtazic Acid/pharmacology
MH  - Extracellular Matrix/*metabolism
MH  - Fibrillins
MH  - Furin
MH  - Microfilament Proteins/*metabolism
MH  - Microscopy, Confocal
MH  - Models, Biological
MH  - Mutagenesis, Site-Directed
MH  - Protein Precursors/*metabolism
MH  - Recombinant Proteins
MH  - Subtilisins/antagonists & inhibitors/*metabolism
MH  - Transforming Growth Factor beta/metabolism
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
PST - ppublish
SO  - J Cell Sci. 1999 Apr;112 ( Pt 7):1093-100.