Linked Life Data

16716076

Source:http://linkedlifedata.com/resource/pubmed/id/16716076

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2006-5-23
pubmed:abstractText
The short cytoplasmic tails regulate activation of integrin adhesion receptors via clasping/unclasping of their membrane-proximal helices. Using integrin alpha(IIb)beta(3) as a model, we show that a previously reported activating mutation alpha(IIb)(R(995)D) that perturbs the electrostatic interface in the clasp only partially activates alpha(IIb)beta(3) and that extensive activation of the receptor is achieved by complete deletion of alpha(IIb) CT or triple mutations in alpha(IIb)(V(990)A/F(992)A/R(995)D) that disrupt both electrostatic and hydrophobic interfaces in the clasp. The results provide quantitative evidence for an equilibrium-based integrin activation process where shifting the equilibrium to the fully activated state requires total unclasping of the cytoplasmic tails. We further demonstrate that while the C-terminal region of the alpha(IIb) tail minimally influences alpha(IIb)beta(3) activation, the C-terminal region of the beta(3) tail is critically involved. A disease-causing mutation of S(752)P in this region, but not S(752)A, suppressed partial activation induced by R(995)D or the talin head domain but did not affect activation induced by alpha(IIb) truncation. NMR spectroscopy revealed that S(752)P but not the S(752)A mutation disrupted a C-terminal helix within the beta(3) tail, suggesting that the C-terminal helix may regulate the equilibrium-based clasping/unclasping process. Together, these data provide molecular insights into how distinct regions of the cytoplasmic tails differentially and cooperatively regulate integrin activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6656-62
pubmed:dateRevised
2011-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Regulation of integrin alphaIIbbeta3 activation by distinct regions of its cytoplasmic tails.
pubmed:affiliation
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural