Linked Life Data

15345710

Source:http://linkedlifedata.com/resource/pubmed/id/15345710

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2004-11-1
pubmed:databankReference
pubmed:abstractText
The molecular mechanisms by which mammalian receptor tyrosine kinases are negatively regulated remain largely unexplored. Previous genetic and biochemical studies indicate that Kekkon-1, a transmembrane protein containing leucine-rich repeats and an immunoglobulin-like domain in its extracellular region, acts as a feedback negative regulator of epidermal growth factor (EGF) receptor signaling in Drosophila melanogaster development. Here we tested whether the related human LRIG1 (also called Lig-1) protein can act as a negative regulator of EGF receptor and its relatives, ErbB2, ErbB3, and ErbB4. We observed that in co-transfected 293T cells, LRIG1 forms a complex with each of the ErbB receptors independent of growth factor binding. We further observed that co-expression of LRIG1 with EGF receptor suppresses cellular receptor levels, shortens receptor half-life, and enhances ligand-stimulated receptor ubiquitination. Finally, we observed that co-expression of LRIG1 suppresses EGF-stimulated transformation of NIH3T3 fibroblasts and that the inducible expression of LRIG1 in PC3 prostate tumor cells suppresses EGF- and neuregulin-1-stimulated cell cycle progression. Our observations indicate that LRIG1 is a negative regulator of the ErbB family of receptor tyrosine kinases and suggest that LRIG1-mediated receptor ubiquitination and degradation may contribute to the suppression of ErbB receptor function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
47050-6
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:15345710-Agar, pubmed-meshheading:15345710-Animals, pubmed-meshheading:15345710-Biotinylation, pubmed-meshheading:15345710-COS Cells, pubmed-meshheading:15345710-Cell Cycle, pubmed-meshheading:15345710-Cell Line, pubmed-meshheading:15345710-Cell Line, Tumor, pubmed-meshheading:15345710-Cloning, Molecular, pubmed-meshheading:15345710-DNA, Complementary, pubmed-meshheading:15345710-Drosophila, pubmed-meshheading:15345710-Fibroblasts, pubmed-meshheading:15345710-Humans, pubmed-meshheading:15345710-Immunoprecipitation, pubmed-meshheading:15345710-Leucine, pubmed-meshheading:15345710-Ligands, pubmed-meshheading:15345710-Membrane Glycoproteins, pubmed-meshheading:15345710-Mice, pubmed-meshheading:15345710-Molecular Sequence Data, pubmed-meshheading:15345710-NIH 3T3 Cells, pubmed-meshheading:15345710-Protein Binding, pubmed-meshheading:15345710-Protein Structure, Tertiary, pubmed-meshheading:15345710-Receptor, Epidermal Growth Factor, pubmed-meshheading:15345710-Receptor, erbB-2, pubmed-meshheading:15345710-Receptor, erbB-3, pubmed-meshheading:15345710-Time Factors, pubmed-meshheading:15345710-Transfection, pubmed-meshheading:15345710-Ubiquitin
pubmed:year
2004
pubmed:articleTitle
The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases.
pubmed:affiliation
University of California Davis Cancer Center, Sacramento, California 95817, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't