JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on July 27, 2001
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
276/31/29538    most recent
M102114200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Brown, C. L.
Right arrow Articles by Dempsey, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, C. L.
Right arrow Articles by Dempsey, P. J.
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?

Papers In Press, published online ahead of print May 29, 2001
J. Biol. Chem, 10.1074/jbc.M102114200
Submitted on March 8, 2001
Revised on May 29, 2001
Accepted on May 29, 2001

ProAmphiregulin cytoplasmic domain is required for basolateral sorting but is not essential for constitutive or stimulus-induced processing in polarized MDCK cells

Christa L. Brown, Robert J. Coffey, and Peter J. Dempsey

Pacific Northwest Research Institute, Seattle, WA 98122

Corresponding Author: pdempsey{at}pnri.org

Previously, we have shown that endogenous amphiregulin precursor (proAR) is expressed on the basolateral cell surface and is constitutively released into the basolateral conditioned medium of two polarizing human colorectal carcinoma (HCA-7, Caco-2) cell lines (1). In this study, the role of the proAR cytoplasmic domain in the basolateral sorting and cell surface processing of proAR in polarized epithelial cells has been investigated using MDCK cells stably expressing various human proAR forms. Our results demonstrate that newly synthesized wild type proAR (50 kDa) is delivered directly to the basolateral membrane domain with greater than 95% efficiency, where it is sequentially cleaved within the ectodomain to release several soluble AR forms. Analyses of a proAR cytoplasmic domain truncation mutant (ARTL27) and two proAR secretory mutants (ARsec184 and ARsec190) indicate that the proAR cytoplasmic domain is not required for efficient delivery to the plasma membrane but does contain essential basolateral sorting information. We show that the proAR cytoplasmic domain truncation mutant (ARTL27) is not sorted in polarized MDCK cells, with ~65% of newly synthesized protein delivered to the apical cell surface. Under baseline conditions, ARTL27 is preferentially cleaved from the basolateral surface with 4-fold greater efficiency as compared to cleavage from the apical membrane domain. However, ARTL27 ectodomain cleavage can be stimulated equivalently from either membrane domain by a variety of different stimuli. The metalloprotease inhibitor BB-94 can inhibit both baseline and stimulus-induced ectodomain cleavage of wild type proAR and ARTL27. These results indicate that although the proAR cytoplasmic domain is required for basolateral sorting but is not essential for ectodomain processing. Preferential constitutive cleavage of ARTL27 from the basolateral cell surface also suggests that the metalloprotease activity involved in baseline and stimulus-induced ARTL27 ectodomain cleavage may be regulated differently at the apical and basolateral membrane domains of polarized epithelial cells.


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
N. E. Willmarth and S. P. Ethier
Autocrine and Juxtacrine Effects of Amphiregulin on the Proliferative, Invasive, and Migratory Properties of Normal and Neoplastic Human Mammary Epithelial Cells
J. Biol. Chem., December 8, 2006; 281(49): 37728 - 37737.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
J. Dong, L. K. Opresko, W. Chrisler, G. Orr, R. D. Quesenberry, D. A. Lauffenburger, and H. S. Wiley
The Membrane-anchoring Domain of Epidermal Growth Factor Receptor Ligands Dictates Their Ability to Operate in Juxtacrine Mode
Mol. Biol. Cell, June 1, 2005; 16(6): 2984 - 2998.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. P. Sanderson, S. N. Erickson, P. J. Gough, K. J. Garton, P. T. Wille, E. W. Raines, A. J. Dunbar, and P. J. Dempsey
ADAM10 Mediates Ectodomain Shedding of the Betacellulin Precursor Activated by p-Aminophenylmercuric Acetate and Extracellular Calcium Influx
J. Biol. Chem., January 21, 2005; 280(3): 1826 - 1837.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Li, J. L. Franklin, R. Graves-Deal, W. G. Jerome, Z. Cao, and R. J. Coffey
Myristoylated Naked2 escorts transforming growth factor {alpha} to the basolateral plasma membrane of polarized epithelial cells
PNAS, April 13, 2004; 101(15): 5571 - 5576.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. W. Sunnarborg, C. L. Hinkle, M. Stevenson, W. E. Russell, C. S. Raska, J. J. Peschon, B. J. Castner, M. J. Gerhart, R. J. Paxton, R. A. Black, et al.
Tumor Necrosis Factor-alpha Converting Enzyme (TACE) Regulates Epidermal Growth Factor Receptor Ligand Availability
J. Biol. Chem., April 5, 2002; 277(15): 12838 - 12845.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.