Linked Life Data

8347619

Source:http://linkedlifedata.com/resource/pubmed/id/8347619

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
1993-9-16
pubmed:abstractText
We have tested one aspect of the allosteric dimerization model for the activation of EGF receptor (EGFR) by EGF: whether EGF binding favors dimerization of the receptor. For this to be true, EGF molecules must bind with higher affinity to dimeric receptors than to monomeric receptors. We have tested this directly in a defined system using the soluble, extracellular ligand binding domain of EGFR monomers (sEGFR) and sEGFR dimers stabilized by treatment with a covalent cross-linking agent. We describe real-time kinetic measurements of EGF binding to receptor monomers and dimers employing the method of total internal reflection (surface plasmon resonance). Our data show that sEGFR dimers bound EGF with 30-40-fold higher affinity [KD = (2-3) x 10(-8) M] than did sEGFR monomers. The enhanced binding affinity of sEGFR dimers resulted mainly from a reduced off-rate with k(off) = 0.001 s-1 for sEGFR dimers as compared to k(off) = 0.06 s-1 for sEGFR monomers. These measurements indicate that dimerization of sEGFR increases its affinity for EGF by prolonging the amount of time that EGF remains bound to the receptor. This provides evidence that EGF binding stabilizes receptor dimerization and provides further support for the allosteric dimerization model as a mechanism for ligand induced receptor activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8193-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation.
pubmed:affiliation
Department of Pharmacology, New York University Medical Center, New York 10016.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't