Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ritty, T. M.
Right arrow Articles by Mecham, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ritty, T. M.
Right arrow Articles by Mecham, R. P.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 274, Issue 13, 8933-8940, March 26, 1999

Processing of the Fibrillin-1 Carboxyl-terminal Domain

Timothy M. RittyDagger , Thomas BroekelmannDagger , Clarina TisdaleDagger , Dianna M. Milewicz§, and Robert P. MechamDagger

From the Dagger  Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110 and the § Department of Internal Medicine, University of Texas-Houston Medical School, Houston, Texas 77030

To investigate the processing and general properties of the fibrillin-1 carboxyl-terminal domain, three protein expression constructs have been developed as follows: one without the domain, one with the domain, and one with a mutation near the putative proteolytic processing site. The constructs have been expressed in two eukaryotic model systems, baculoviral and CHO-K1. Post-translational modifications that normally occur in fibrillin-1, including glycosylation, signal peptide cleavage, and carboxyl-terminal processing, occur in the three constructs in both cell systems. Amino-terminal sequencing of secreted protein revealed leader sequence processing at two sites, a primary site between Gly-24/Ala-25 and a secondary site of Ala-27/Asn-28. Processing of the carboxyl-terminal domain could be observed by migration differences in SDS-polyacrylamide gel electrophoresis and was evident in both mammalian and insect cells. Immunological identification by Western blotting confirmed the loss of the expected region. The failure of both cell systems to process the mutant construct shows that the multi-basic sequence is the site of proteolytic processing. Cleavage of the fibrillin-1 carboxyl-terminal domain occurred intracellularly in CHO-K1 cells in an early secretory pathway compartment as demonstrated by studies with secretion blocking agents. This finding, taken with the multi-basic nature of the cleavage site and observed calcium sensitivity of cleavage, suggests that the processing enzyme is a secretory pathway resident furin-like protease.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
J. S. Weinbaum, T. J. Broekelmann, R. A. Pierce, C. C. Werneck, F. Segade, C. S. Craft, R. H. Knutsen, and R. P. Mecham
Deficiency in Microfibril-associated Glycoprotein-1 Leads to Complex Phenotypes in Multiple Organ Systems
J. Biol. Chem., September 12, 2008; 283(37): 25533 - 25543.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Cell Mol. Bio.Home page
S. E. McGowan, A. J. Holmes, R. P. Mecham, and T. M. Ritty
Arg-Gly-Asp-Containing Domains of Fibrillins-1 and -2 Distinctly Regulate Lung Fibroblast Migration
Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 435 - 445.
[Abstract] [Full Text] [PDF]


Home page
J. Med. Genet.Home page
P N Robinson, E Arteaga-Solis, C Baldock, G Collod-Beroud, P Booms, A De Paepe, H C Dietz, G Guo, P A Handford, D P Judge, et al.
The molecular genetics of Marfan syndrome and related disorders
J. Med. Genet., October 1, 2006; 43(10): 769 - 787.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. Hubmacher, K. Tiedemann, R. Bartels, J. Brinckmann, T. Vollbrandt, B. Batge, H. Notbohm, and D. P. Reinhardt
Modification of the Structure and Function of Fibrillin-1 by Homocysteine Suggests a Potential Pathogenetic Mechanism in Homocystinuria
J. Biol. Chem., October 14, 2005; 280(41): 34946 - 34955.
[Abstract] [Full Text] [PDF]


Home page
Hum Mol GenetHome page
S. Hutchinson, A. Furger, D. Halliday, D. P. Judge, A. Jefferson, H. C. Dietz, H. Firth, and P. A. Handford
Allelic variation in normal human FBN1 expression in a family with Marfan syndrome: a potential modifier of phenotype?
Hum. Mol. Genet., September 15, 2003; 12(18): 2269 - 2276.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
B. A. Kozel, H. Wachi, E. C. Davis, and R. P. Mecham
Domains in Tropoelastin That Mediate Elastin Deposition in Vitro and in Vivo
J. Biol. Chem., May 9, 2003; 278(20): 18491 - 18498.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
G. Lin, K. Tiedemann, T. Vollbrandt, H. Peters, B. Batge, J. Brinckmann, and D. P. Reinhardt
Homo- and Heterotypic Fibrillin-1 and -2 Interactions Constitute the Basis for the Assembly of Microfibrils
J. Biol. Chem., December 20, 2002; 277(52): 50795 - 50804.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
C. M. Kielty, M. J. Sherratt, and C. A. Shuttleworth
Elastic fibres
J. Cell Sci., July 15, 2002; 115(14): 2817 - 2828.
[Abstract] [Full Text] [PDF]


Home page
Hum Mol GenetHome page
S. S. Chaudhry, J. Gazzard, C. Baldock, J. Dixon, M. J. Rock, G. C. Skinner, K. P. Steel, C. M. Kielty, and M. J. Dixon
Mutation of the gene encoding fibrillin-2 results in syndactyly in mice
Hum. Mol. Genet., April 1, 2001; 10(8): 835 - 843.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
C. Baldock, A. J. Koster, U. Ziese, M. J. Rock, M. J. Sherratt, K. E. Kadler, C. A. Shuttleworth, and C. M. Kielty
The Supramolecular Organization of Fibrillin-rich Microfibrils
J. Cell Biol., March 5, 2001; 152(5): 1045 - 1056.
[Abstract] [Full Text] [PDF]


Home page
Br. J. Ophthalmol.Home page
J. L ASHWORTH, C. M KIELTY, and D. McLEOD
Fibrillin and the eye
Br. J. Ophthalmol., November 1, 2000; 84(11): 1312 - 1317.
[Full Text] [PDF]


Home page
Hum Mol GenetHome page
A. J. McGettrick, V. Knott, A. Willis, and P. A. Handford
Molecular effects of calcium binding mutations in Marfan syndrome depend on domain context
Hum. Mol. Genet., August 12, 2000; 9(13): 1987 - 1994.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
B. C. Trask, T. M. Trask, T. Broekelmann, and R. P. Mecham
The Microfibrillar Proteins MAGP-1 and Fibrillin-1 Form a Ternary Complex with the Chondroitin Sulfate Proteoglycan Decorin
Mol. Biol. Cell, May 1, 2000; 11(5): 1499 - 1507.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
D. P. Reinhardt, J. E. Gambee, R. N. Ono, H. P. Bachinger, and L. Y. Sakai
Initial Steps in Assembly of Microfibrils. FORMATION OF DISULFIDE-CROSS-LINKED MULTIMERS CONTAINING FIBRILLIN-1
J. Biol. Chem., January 21, 2000; 275(3): 2205 - 2210.
[Abstract] [Full Text] [PDF]


Home page
J. Med. Genet.Home page
P. N Robinson and M. Godfrey
The molecular genetics of Marfan syndrome and related microfibrillopathies
J. Med. Genet., January 1, 2000; 37(1): 9 - 25.
[Abstract] [Full Text]


Home page
J. Cell Sci.Home page
J. Ashworth, V Kelly, M. Rock, C. Shuttleworth, and C. Kielty
Regulation of fibrillin carboxy-terminal furin processing by N-glycosylation, and association of amino- and carboxy-terminal sequences
J. Cell Sci., January 11, 1999; 112(22): 4163 - 4171.
[Abstract] [PDF]


Home page
J. Cell Sci.Home page
J. Ashworth, V Kelly, R Wilson, C. Shuttleworth, and C. Kielty
Fibrillin assembly: dimer formation mediated by amino-terminal sequences
J. Cell Sci., January 10, 1999; 112(20): 3549 - 3558.
[Abstract] [PDF]


Home page
J. Biol. Chem.Home page
T. M. Trask, B. C. Trask, T. M. Ritty, W. R. Abrams, J. Rosenbloom, and R. P. Mecham
Interaction of Tropoelastin with the Amino-terminal Domains of Fibrillin-1 and Fibrillin-2 Suggests a Role for the Fibrillins in Elastic Fiber Assembly
J. Biol. Chem., August 4, 2000; 275(32): 24400 - 24406.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement