No Cover Image

Journal article 401 views

The UIM domain of Hrs couples receptor sorting to vesicle formation / Paula, Row

Journal of Cell Science, Volume: 116, Issue: 20, Pages: 4169 - 4179

Swansea University Author: Paula, Row

Full text not available from this repository: check for access using links below.

DOI (Published version): 10.1242/jcs.00723

Abstract

Hepatocyte growth factor regulated tyrosine kinase substrate (Hrs), a main component of the 'bilayered' clathrin coat on sorting endosomes, was originally identified as a substrate of activated tyrosine kinase receptors. We have analysed Hrs phosphorylation in response to epidermal growth...

Full description

Published in: Journal of Cell Science
Published: 2003
Online Access: http://jcs.biologists.org/content/116/20/4169.full.pdf
URI: https://cronfa.swan.ac.uk/Record/cronfa18377
Tags: Add Tag
No Tags, Be the first to tag this record!
first_indexed 2014-09-11T01:59:10Z
last_indexed 2019-06-24T19:28:50Z
id cronfa18377
recordtype SURis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2019-06-24T15:13:40.1219668</datestamp><bib-version>v2</bib-version><id>18377</id><entry>2014-09-10</entry><title>The UIM domain of Hrs couples receptor sorting to vesicle formation</title><swanseaauthors><author><sid>99bb528b2f8fb62aabbdad101d53ba96</sid><firstname>Paula</firstname><surname>Row</surname><name>Paula Row</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2014-09-10</date><deptcode>BMS</deptcode><abstract>Hepatocyte growth factor regulated tyrosine kinase substrate (Hrs), a main component of the 'bilayered' clathrin coat on sorting endosomes, was originally identified as a substrate of activated tyrosine kinase receptors. We have analysed Hrs phosphorylation in response to epidermal growth factor (EGF) stimulation and show that the evolutionary conserved tyrosines Y329 and Y334 provide the principal phosphorylation sites. Hrs is proposed to concentrate ubiquitinated receptors within clathrin-coated regions via direct interaction with its UIM (ubiquitin interaction motif) domain. We show that the same UIM domain is necessary for EGF-stimulated tyrosine phosphorylation of Hrs. Over-expression of wild-type Hrs or a double mutant, Y329/334F, defective in EGF-dependent phosphorylation, both substantially retard EGF receptor (EGFR) degradation by inhibiting internal vesicle formation and thereby preventing EGFR incorporation into lumenal vesicles of the multivesicular bodies. In contrast, mutation or deletion of the Hrs-UIM domain strongly suppresses this effect. In addition the UIM-deletion and point mutants are also observed on internal membranes, indicating a failure to dissociate from the endosomal membrane prior to incorporation of the receptor complex into lumenal vesicles. Our data suggest a role for the UIM-domain of Hrs in actively retaining EGFR at the limiting membrane of endosomes as a prelude to lumenal vesicle formation.</abstract><type>Journal Article</type><journal>Journal of Cell Science</journal><volume>116</volume><journalNumber>20</journalNumber><paginationStart>4169</paginationStart><paginationEnd>4179</paginationEnd><publisher/><keywords>Hrs, Endocytosis, Clathrin, Ubiquitin, Phosphorylation</keywords><publishedDay>12</publishedDay><publishedMonth>9</publishedMonth><publishedYear>2003</publishedYear><publishedDate>2003-09-12</publishedDate><doi>10.1242/jcs.00723</doi><url>http://jcs.biologists.org/content/116/20/4169.full.pdf</url><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><lastEdited>2019-06-24T15:13:40.1219668</lastEdited><Created>2014-09-10T13:34:53.1892203</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>S.</firstname><surname>Urbe</surname><order>1</order></author><author><firstname>Martin</firstname><surname>Sachse</surname><order>2</order></author><author><firstname>Paula</firstname><surname>Row</surname><order>3</order></author><author><firstname>Christian</firstname><surname>Preisinger</surname><order>4</order></author><author><firstname>Francis A</firstname><surname>Barr</surname><order>5</order></author><author><firstname>Ger</firstname><surname>Strous</surname><order>6</order></author><author><firstname>Judith</firstname><surname>Klumperman</surname><order>7</order></author><author><firstname>Michael J</firstname><surname>Clague</surname><order>8</order></author></authors><documents><document><type>Output</type><version>Not Applicable (or Unknown)</version><cronfaStatus>true</cronfaStatus><action/><embargoDate>2014-09-09T00:00:00.0000000</embargoDate><documentNotes/><copyrightCorrect>false</copyrightCorrect></document></documents></rfc1807>
spelling 2019-06-24T15:13:40.1219668 v2 18377 2014-09-10 The UIM domain of Hrs couples receptor sorting to vesicle formation 99bb528b2f8fb62aabbdad101d53ba96 Paula Row Paula Row true false 2014-09-10 BMS Hepatocyte growth factor regulated tyrosine kinase substrate (Hrs), a main component of the 'bilayered' clathrin coat on sorting endosomes, was originally identified as a substrate of activated tyrosine kinase receptors. We have analysed Hrs phosphorylation in response to epidermal growth factor (EGF) stimulation and show that the evolutionary conserved tyrosines Y329 and Y334 provide the principal phosphorylation sites. Hrs is proposed to concentrate ubiquitinated receptors within clathrin-coated regions via direct interaction with its UIM (ubiquitin interaction motif) domain. We show that the same UIM domain is necessary for EGF-stimulated tyrosine phosphorylation of Hrs. Over-expression of wild-type Hrs or a double mutant, Y329/334F, defective in EGF-dependent phosphorylation, both substantially retard EGF receptor (EGFR) degradation by inhibiting internal vesicle formation and thereby preventing EGFR incorporation into lumenal vesicles of the multivesicular bodies. In contrast, mutation or deletion of the Hrs-UIM domain strongly suppresses this effect. In addition the UIM-deletion and point mutants are also observed on internal membranes, indicating a failure to dissociate from the endosomal membrane prior to incorporation of the receptor complex into lumenal vesicles. Our data suggest a role for the UIM-domain of Hrs in actively retaining EGFR at the limiting membrane of endosomes as a prelude to lumenal vesicle formation. Journal Article Journal of Cell Science 116 20 4169 4179 Hrs, Endocytosis, Clathrin, Ubiquitin, Phosphorylation 12 9 2003 2003-09-12 10.1242/jcs.00723 http://jcs.biologists.org/content/116/20/4169.full.pdf COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-06-24T15:13:40.1219668 2014-09-10T13:34:53.1892203 Swansea University Medical School Medicine S. Urbe 1 Martin Sachse 2 Paula Row 3 Christian Preisinger 4 Francis A Barr 5 Ger Strous 6 Judith Klumperman 7 Michael J Clague 8 Output Not Applicable (or Unknown) true 2014-09-09T00:00:00.0000000 false
title The UIM domain of Hrs couples receptor sorting to vesicle formation
spellingShingle The UIM domain of Hrs couples receptor sorting to vesicle formation
Paula, Row
title_short The UIM domain of Hrs couples receptor sorting to vesicle formation
title_full The UIM domain of Hrs couples receptor sorting to vesicle formation
title_fullStr The UIM domain of Hrs couples receptor sorting to vesicle formation
title_full_unstemmed The UIM domain of Hrs couples receptor sorting to vesicle formation
title_sort The UIM domain of Hrs couples receptor sorting to vesicle formation
author_id_str_mv 99bb528b2f8fb62aabbdad101d53ba96
author_id_fullname_str_mv 99bb528b2f8fb62aabbdad101d53ba96_***_Paula, Row
author Paula, Row
format Journal article
container_title Journal of Cell Science
container_volume 116
container_issue 20
container_start_page 4169
publishDate 2003
institution Swansea University
doi_str_mv 10.1242/jcs.00723
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
url http://jcs.biologists.org/content/116/20/4169.full.pdf
document_store_str 0
active_str 0
description Hepatocyte growth factor regulated tyrosine kinase substrate (Hrs), a main component of the 'bilayered' clathrin coat on sorting endosomes, was originally identified as a substrate of activated tyrosine kinase receptors. We have analysed Hrs phosphorylation in response to epidermal growth factor (EGF) stimulation and show that the evolutionary conserved tyrosines Y329 and Y334 provide the principal phosphorylation sites. Hrs is proposed to concentrate ubiquitinated receptors within clathrin-coated regions via direct interaction with its UIM (ubiquitin interaction motif) domain. We show that the same UIM domain is necessary for EGF-stimulated tyrosine phosphorylation of Hrs. Over-expression of wild-type Hrs or a double mutant, Y329/334F, defective in EGF-dependent phosphorylation, both substantially retard EGF receptor (EGFR) degradation by inhibiting internal vesicle formation and thereby preventing EGFR incorporation into lumenal vesicles of the multivesicular bodies. In contrast, mutation or deletion of the Hrs-UIM domain strongly suppresses this effect. In addition the UIM-deletion and point mutants are also observed on internal membranes, indicating a failure to dissociate from the endosomal membrane prior to incorporation of the receptor complex into lumenal vesicles. Our data suggest a role for the UIM-domain of Hrs in actively retaining EGFR at the limiting membrane of endosomes as a prelude to lumenal vesicle formation.
published_date 2003-09-12T18:31:24Z
_version_ 1650656054445342720
score 10.8683