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Systematic mutational analysis of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor cytoplasmic domain - An acidic cluster containing a key aspartate is important for function in lysosomal enzyme sorting

Chen, Hong Jung and Yuan, Jing and Lobel, Peter (1997) Systematic mutational analysis of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor cytoplasmic domain - An acidic cluster containing a key aspartate is important for function in lysosomal enzyme sorting. Journal of Biological Chemistry, 272 (11). pp. 7003-7012. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:CHEjbc97

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Abstract

We have used systematic mutational analysis to identify signals in the 166-residue murine cation-independent mannose 6-phosphate/insulin-like growth factor II receptor cytoplasmic domain required for efficient sorting of lysosomal enzymes. Alanine cluster mutagenesis on all conserved residues apart from the endocytosis signal demonstrates that the major sorting determinant is a conserved casein kinase II site followed by a dileucine motif (157DDSDEDLL164). Small deletions or additions outside this region have severe to mild effects, indicating that context is important. Single residue mutagenesis indicates that cycles of serine phosphorylation/dephosphorylation are not obligatory for sorting. In addition, the two leucine residues and four of the five negatively charged residues can readily tolerate conservative substitutions. In contrast, aspartate 160 could not tolerate isoelectric or isosteric substitutions, implicating it as a critical component of the sorting signal.


Item Type:Article
Additional Information:©1997 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, August 13, 1996, and in revised form, December 27, 1996. We thank Jill Remmler for technical assistance and Li Lin and David Sleat for critical reading of the manuscript. This work was supported by National Institutes of Health Grant DK-45992. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Subject Keywords:TRANS-GOLGI NETWORK; DI-LEUCINE MOTIF; GLUT4 GLUCOSE-TRANSPORTER; LEU-LEU SEQUENCE; 6-PHOSPHATE RECEPTOR; CELL-SURFACE; RAPID INTERNALIZATION; CARBOXYL-TERMINUS; ENDOCYTIC PATHWAY; FC-RECEPTORS
Record Number:CaltechAUTHORS:CHEjbc97
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:CHEjbc97
Alternative URL:http://www.jbc.org/cgi/content/abstract/272/11/7003
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:3760
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:10 Jul 2006
Last Modified:26 Dec 2012 08:56

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