JBC Focus on PI3-Kinase with Echelon

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


     

Originally published In Press as doi:10.1074/jbc.M011414200 on January 22, 2001

J. Biol. Chem., Vol. 276, Issue 16, 13248-13255, April 20, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/16/13248    most recent
M011414200v1
Right arrow Alert me when this article is cited
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bertenshaw, G. P.
Right arrow Articles by Bond, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bertenshaw, G. P.
Right arrow Articles by Bond, J. S.
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?

Marked Differences between Metalloproteases Meprin A and B in Substrate and Peptide Bond Specificity*

Greg P. BertenshawDagger , Benjamin E. Turk§, Simon J. Hubbard||, Gail L. MattersDagger , John E. BylanderDagger , Jacqueline M. CrismanDagger , Lewis C. Cantley§, and Judith S. BondDagger **

From the Dagger  Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, the § Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, the  Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, and the || Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, United Kingdom

Meprin A and B are highly regulated, secreted, and cell-surface metalloendopeptidases that are abundantly expressed in the kidney and intestine. Meprin oligomers consist of evolutionarily related alpha  and/or beta  subunits. The work herein was carried out to identify bioactive peptides and proteins that are susceptible to hydrolysis by mouse meprins and kinetically characterize the hydrolysis. Gastrin-releasing peptide fragment 14-27 and gastrin 17, regulatory molecules of the gastrointestinal tract, were found to be the best peptide substrates for meprin A and B, respectively. Peptide libraries and a variety of naturally occurring peptides revealed that the meprin beta  subunit has a clear preference for acidic amino acids in the P1 and P1' sites of substrates. The meprin alpha  subunit selected for small (e.g. serine, alanine) or hydrophobic (e.g. phenylalanine) residues in the P1 and P1' sites, and proline was the most preferred amino acid at the P2' position. Thus, although the meprin alpha  and beta  subunits share 55% amino acid identity within the protease domain and are normally localized at the same tissue cell surfaces, they have very different substrate and peptide bond specificities indicating different functions. Homology models of the mouse meprin alpha  and beta  protease domains, based on the astacin crystal structure, revealed active site differences that can account for the marked differences in substrate specificity of the two subunits.

* This work was supported by the American Heart Association Predoctoral Fellowship 9910075U (to G. P. B.), by Department of Defense Grant DAMD17-98-1-8143 (to G. L. M.), and by National Institutes of Health Grants DK19691 and DK54625 (to J. S. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, H171, The Pennsylvania State University College of Medicine, Hershey, PA 17033-0850. Tel.: 717-531-8586; Fax: 717-531-7072; E-mail: jbond@psu.edu.

Copyright © 2001 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
D. A. Bergin, C. M. Greene, E. E. Sterchi, C. Kenna, P. Geraghty, A. Belaaouaj, C. C. Taggart, S. J. O'Neill, and N. G. McElvaney
Activation of the Epidermal Growth Factor Receptor (EGFR) by a Novel Metalloprotease Pathway
J. Biol. Chem., November 14, 2008; 283(46): 31736 - 31744.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Banerjee and J. S. Bond
Prointerleukin-18 Is Activated by Meprin {beta} in Vitro and in Vivo in Intestinal Inflammation
J. Biol. Chem., November 14, 2008; 283(46): 31371 - 31377.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Bylander, Q. Li, G. Ramesh, B. Zhang, W. B. Reeves, and J. S. Bond
Targeted disruption of the meprin metalloproteinase {beta} gene protects against renal ischemia-reperfusion injury in mice
Am J Physiol Renal Physiol, March 1, 2008; 294(3): F480 - F490.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
K. Pankow, Y. Wang, F. Gembardt, E. Krause, X. Sun, G. Krause, H.-P. Schultheiss, W.-E. Siems, and T. Walther
Successive Action of Meprin A and Neprilysin Catabolizes B-Type Natriuretic Peptide
Circ. Res., October 26, 2007; 101(9): 875 - 882.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Hirano, B. Y. Ma, N. Kawasaki, K. Okimura, M. Baba, T. Nakagawa, K. Miwa, N. Kawasaki, S. Oka, and T. Kawasaki
Mannan-Binding Protein Blocks the Activation of Metalloproteases Meprin {alpha} and {beta}
J. Immunol., September 1, 2005; 175(5): 3177 - 3185.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. T. Ishmael, V. K. Shier, S. S. Ishmael, and J. S. Bond
Intersubunit and Domain Interactions of the Meprin B Metalloproteinase: DISULFIDE BONDS AND PROTEIN-PROTEIN INTERACTIONS IN THE MAM AND TRAF DOMAINS
J. Biol. Chem., April 8, 2005; 280(14): 13895 - 13901.
[Abstract] [Full Text] [PDF]

Home page
 Plant Physiol.Home page
H. Weber, A. Bernhardt, M. Dieterle, P. Hano, A. Mutlu, M. Estelle, P. Genschik, and H. Hellmann
Arabidopsis AtCUL3a and AtCUL3b Form Complexes with Members of the BTB/POZ-MATH Protein Family
Plant Physiology, January 1, 2005; 137(1): 83 - 93.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. M. Crisman, B. Zhang, L. P. Norman, and J. S. Bond
Deletion of the Mouse Meprin {beta} Metalloprotease Gene Diminishes the Ability of Leukocytes to Disseminate through Extracellular Matrix
J. Immunol., April 1, 2004; 172(7): 4510 - 4519.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Hahn, A. Pischitzis, S. Roesmann, M. K. Hansen, B. Leuenberger, U. Luginbuehl, and E. E. Sterchi
Phorbol 12-Myristate 13-Acetate-induced Ectodomain Shedding and Phosphorylation of the Human Meprin{beta} Metalloprotease
J. Biol. Chem., October 31, 2003; 278(44): 42829 - 42839.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. P. Villa, G. P. Bertenshaw, and J. S. Bond
Critical Amino Acids in the Active Site of Meprin Metalloproteinases for Substrate and Peptide Bond Specificity
J. Biol. Chem., October 24, 2003; 278(43): 42545 - 42550.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L. P. Norman, W. Jiang, X. Han, T. L. Saunders, and J. S. Bond
Targeted Disruption of the Meprin {beta} Gene in Mice Leads to Underrepresentation of Knockout Mice and Changes in Renal Gene Expression Profiles
Mol. Cell. Biol., February 15, 2003; 23(4): 1221 - 1230.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. P. Bertenshaw, M. T. Norcum, and J. S. Bond
Structure of Homo- and Hetero-oligomeric Meprin Metalloproteases. DIMERS, TETRAMERS, AND HIGH MOLECULAR MASS MULTIMERS
J. Biol. Chem., January 17, 2003; 278(4): 2522 - 2532.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Rosmann, D. Hahn, D. Lottaz, M.-N. Kruse, W. Stocker, and E. E. Sterchi
Activation of Human Meprin-alpha in a Cell Culture Model of Colorectal Cancer Is Triggered by the Plasminogen-activating System
J. Biol. Chem., October 18, 2002; 277(43): 40650 - 40658.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
M. A. Riehle, S. F. Garczynski, J. W. Crim, C. A. Hill, and M. R. Brown
Neuropeptides and Peptide Hormones in Anopheles gambiae
Science, October 4, 2002; 298(5591): 172 - 175.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Litovchick, E. Friedmann, and S. Shaltiel
A Selective Interaction between OS-9 and the Carboxyl-terminal Tail of Meprin beta
J. Biol. Chem., September 6, 2002; 277(37): 34413 - 34423.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. T. Ishmael, M. T. Norcum, S. J. Benkovic, and J. S. Bond
Multimeric Structure of the Secreted Meprin A Metalloproteinase and Characterization of the Functional Protomer
J. Biol. Chem., June 15, 2001; 276(25): 23207 - 23211.
[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 © 2001 by the American Society for Biochemistry and Molecular Biology.