Del Vecchio, R. L., Tonks, N. K. (January 2005) The conserved immunoglobulin domain controls the subcellular localization of the homophilic adhesion receptor protein-tyrosine phosphatase mu. J Biol Chem, 280 (2). pp. 1603-12. ISSN 0021-9258 (Print)
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Abstract
The receptor protein-tyrosine phosphatase mu (PTPmu) is a homophilic adhesion protein thought to regulate cell-cell adhesion in the vascular endothelium through dephosphorylation of cell junction proteins. In subconfluent cell cultures, PTPmu resides in an intracellular membrane pool; however, as culture density increases and cell contacts form, the phosphatase localizes to sites of cell-cell contact, and its expression level increases. These characteristics of PTPmu, which are consistent with a role in cell-cell adhesion, suggest that control of subcellular localization is an important mechanism to regulate the function of this phosphatase. To gain a better understanding of how PTPmu is regulated, we examined the importance of the conserved immunoglobulin domain, containing the homophilic binding site, in control of the localization of the enzyme. Deletion of the immunoglobulin domain impaired localization of PTPmu to the cell-cell contacts in endothelial and epithelial cells. In addition, deletion of the immunoglobulin domain affected the distribution of PTPmu in subconfluent endothelial cells when homophilic binding to another PTPmu molecule on an apposing cell was not possible, resulting in an accumulation of the mutant phosphatase at the cell surface with a concentration at the cell periphery in the region occupied by focal adhesions. This aberrant localization correlated with reduced survival and alterations in normal focal adhesion and cytoskeleton morphology. This study therefore illustrates the critical role of the immunoglobulin domain in regulation of the localization of PTPmu and the importance of such control for the maintenance of normal cell physiology.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Cattle Cell Adhesion Cell Line Cell Membrane enzymology metabolism Cell Polarity Cell Survival Conserved Sequence Dogs Focal Adhesions Gene Deletion Humans Immunoglobulins chemistry Phosphotyrosine metabolism Protein Structure Tertiary Protein Transport Protein-Tyrosine-Phosphatase chemistry deficiency genetics metabolism Stress Fibers enzymology metabolism Vinculin metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase |
| CSHL Authors: | |
| Communities: | CSHL labs > Tonks lab |
| Depositing User: | CSHL Librarian |
| Date: | 14 January 2005 |
| Date Deposited: | 13 Jan 2012 20:35 |
| Last Modified: | 21 Feb 2017 20:47 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22552 |
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