Source:http://linkedlifedata.com/resource/pubmed/id/20580638
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
14
|
| pubmed:dateCreated |
2010-7-12
|
| pubmed:abstractText |
Like many other receptor tyrosine kinases (RTKs), platelet-derived growth factor (PDGF) receptor beta (PDGFR-beta) is internalized and degraded in lysosomes in response to PDGF stimulation, which regulates many aspects of cell signalling. However, little is known about the regulation of PDGFR-beta endocytosis. Given that ligand binding is essential for the rapid internalization of RTKs, the events induced by the ligand binding likely contribute to the regulation of ligand-induced RTK internalization. These events include receptor dimerization, activation of intrinsic tyrosine kinase activity and autophosphorylation. In this communication, we examined the role of PDGFR-beta kinase activity, PDGFR-beta dimerization and PDGFR-beta C-terminal motifs in PDGF-induced PDGFR-beta internalization. We showed that inhibition of PDGFR-beta kinase activity by chemical inhibitor or mutation did not block PDGF-induced PDGFR-beta endocytosis, suggesting that the kinase activity is not essential. We further showed that dimerization of PDGFR-beta is essential and sufficient to drive PDGFR-beta internalization independent of PDGFR-beta kinase activation. Moreover, we showed that the previously reported 14 amino acid sequence 952-965 is required for PDGF-induced PDGFR-beta internalization. Most importantly, we showed that this PDGFR-beta internalization motif is exchangeable with the EGFR internalization motif (1005-1017) in mediating ligand-induced internalization of both PDGFR-beta and EGFR. This indicates a common mechanism for the internalization of both PDGFR-beta and EGFR.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1090-2422
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
316
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2237-50
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:20580638-Amino Acid Motifs,
pubmed-meshheading:20580638-Amino Acid Sequence,
pubmed-meshheading:20580638-Animals,
pubmed-meshheading:20580638-Cell Line,
pubmed-meshheading:20580638-Dimerization,
pubmed-meshheading:20580638-Endocytosis,
pubmed-meshheading:20580638-Enzyme Activation,
pubmed-meshheading:20580638-Enzyme Inhibitors,
pubmed-meshheading:20580638-Flow Cytometry,
pubmed-meshheading:20580638-Fluorescent Antibody Technique,
pubmed-meshheading:20580638-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:20580638-Mice,
pubmed-meshheading:20580638-Molecular Sequence Data,
pubmed-meshheading:20580638-NIH 3T3 Cells,
pubmed-meshheading:20580638-Phosphotransferases,
pubmed-meshheading:20580638-Receptor, Epidermal Growth Factor,
pubmed-meshheading:20580638-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:20580638-Sequence Alignment
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Dimerization drives PDGF receptor endocytosis through a C-terminal hydrophobic motif shared by EGF receptor.
|
| pubmed:affiliation |
Department of Cell Biology and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|