Identification of the minimal lysosomal enzyme recognition domain in cathepsin D

doi:10.1074/jbc.M505994200

HOME

QUICK SEARCH:

	Author:		Keyword(s):
Year:		Vol:		Page:

A more recent version of this article appeared on September 30, 2005

This Article

	Full Text (Accepted Manuscript)
	All Versions of this Article: 280/39/33318 most recent M505994200v1
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Request Permissions

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Steet, R.
	Articles by Kornfeld, S.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Steet, R.
	Articles by Kornfeld, S.

Social Bookmarking

	What's this?

Papers In Press, published online ahead of print August 4, 2005
J. Biol. Chem, 10.1074/jbc.M505994200
Submitted on June 1, 2005
Accepted on August 4, 2005

Identification of the minimal lysosomal enzyme recognition domain in cathepsin D

Richard Steet, Wang-Sik Lee, and Stuart Kornfeld

Department of Medicine, Washington University, St. Louis, MO 63110

Corresponding Author: skornfel{at}im.wustl.edu

Specific recognition of lysosomal hydrolases by UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the initial enzyme in the biosynthesis of mannose 6-phosphate residues, is governed by a common protein determinant. Previously, we generated a lysosomal enzyme recognition domain in the secretory protein glycopepsinogen by substituting in two regions (lysine 203 and amino acids 265-293 of the ß loop) from cathepsin D, a highly related lysosomal protease. Here we show that substitution of just two lysines (Lys-203 and Lys-267) stimulates mannose phosphorylation 116-fold. Substitution of additional residues in the ß loop, particularly lysines, increased phosphorylation 4-fold further, approaching the level obtained with intact cathepsin D. All the phosphorylation occurred at the carboxyl lobe glycan, indicating that additional elements are required for phosphorylation of the amino lobe glycan. These data support the proposal that as few as two lysines in the correct orientation to each other and to the glycan can serve as the minimal elements of the lysosomal enzyme recognition domain. However, our findings show that the spacing between lysines is flexible and other residues contribute to the recognition marker.

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:

N. M Dahms, L. J Olson, and J.-J. P Kim
Strategies for carbohydrate recognition by the mannose 6-phosphate receptors
Glycobiology, September 1, 2008; 18(9): 664 - 678.
[Abstract] [Full Text] [PDF]

E. Miller, D. Fiete, N. M. J. Blake, M. Beranek, E. L. Oates, Y. Mi, D. S. Roseman, and J. U. Baenziger
A Necessary and Sufficient Determinant for Protein-selective Glycosylation in Vivo
J. Biol. Chem., January 25, 2008; 283(4): 1985 - 1991.
[Abstract] [Full Text] [PDF]

W.-S. Lee, B. J. Payne, C. M. Gelfman, P. Vogel, and S. Kornfeld
Murine UDP-GlcNAc:Lysosomal Enzyme N-Acetylglucosamine-1-phosphotransferase Lacking the {gamma}-Subunit Retains Substantial Activity toward Acid Hydrolases
J. Biol. Chem., September 14, 2007; 282(37): 27198 - 27203.
[Abstract] [Full Text] [PDF]

D. E. Sleat, H. Zheng, M. Qian, and P. Lobel
Identification of Sites of Mannose 6-Phosphorylation on Lysosomal Proteins
Mol. Cell. Proteomics, April 1, 2006; 5(4): 686 - 701.
[Abstract] [Full Text] [PDF]