Linked Life Data

10827173

Source:http://linkedlifedata.com/resource/pubmed/id/10827173

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2000-9-21
pubmed:abstractText
The members of the low density lipoprotein (LDL) receptor gene family bind a broad spectrum of extracellular ligands. Traditionally, they had been regarded as mere cargo receptors that promote the endocytosis and lysosomal delivery of these ligands. However, recent genetic experiments in mice have revealed critical functions for two LDL receptor family members, the very low density lipoprotein receptor and the apoE receptor-2, in the transmission of extracellular signals and the activation of intracellular tyrosine kinases. This process regulates neuronal migration and is crucial for brain development. Signaling through these receptors requires the interaction of their cytoplasmic tails with the intracellular adaptor protein Disabled-1 (DAB1). Here, we identify an extended set of cytoplasmic proteins that might also participate in signal transmission by the LDL receptor gene family. Most of these novel proteins are adaptor or scaffold proteins that contain PID or PDZ domains and function in the regulation of mitogen-activated protein kinases, cell adhesion, vesicle trafficking, or neurotransmission. We show that binding of DAB1 interferes with receptor internalization suggesting a mechanism by which signaling through this class of receptors might be regulated. Taken together, these findings imply much broader physiological functions for the LDL receptor family than had previously been appreciated. They form the basis for the elucidation of the molecular pathways by which cells respond to the diversity of ligands that bind to these multifunctional receptors on the cell surface.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25616-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10827173-Amino Acid Sequence, pubmed-meshheading:10827173-Animals, pubmed-meshheading:10827173-Brain, pubmed-meshheading:10827173-Cell Adhesion, pubmed-meshheading:10827173-Cell Communication, pubmed-meshheading:10827173-Cells, Cultured, pubmed-meshheading:10827173-Cytosol, pubmed-meshheading:10827173-DNA Primers, pubmed-meshheading:10827173-Endocytosis, pubmed-meshheading:10827173-Glutathione Transferase, pubmed-meshheading:10827173-In Situ Hybridization, pubmed-meshheading:10827173-Kidney, pubmed-meshheading:10827173-Lipoproteins, LDL, pubmed-meshheading:10827173-Liver, pubmed-meshheading:10827173-Mice, pubmed-meshheading:10827173-Models, Biological, pubmed-meshheading:10827173-Molecular Sequence Data, pubmed-meshheading:10827173-Multigene Family, pubmed-meshheading:10827173-Nerve Tissue Proteins, pubmed-meshheading:10827173-Plasmids, pubmed-meshheading:10827173-Protein Structure, Tertiary, pubmed-meshheading:10827173-Receptors, LDL, pubmed-meshheading:10827173-Recombinant Fusion Proteins, pubmed-meshheading:10827173-Sequence Homology, Amino Acid, pubmed-meshheading:10827173-Signal Transduction, pubmed-meshheading:10827173-Time Factors, pubmed-meshheading:10827173-Two-Hybrid System Techniques
pubmed:year
2000
pubmed:articleTitle
Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction.
pubmed:affiliation
Department of Molecular Genetics and Pathology, University of Texas Southwestern Medical Center, Dallas 75390-9046, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't