Linked Life Data

21362552

Source:http://linkedlifedata.com/resource/pubmed/id/21362552

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-3-2
pubmed:databankReference
pubmed:abstractText
Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. The structure of a p110?/p85? complex identifies an inhibitory function for the C-terminal SH2 domain (cSH2) of the p85 regulatory subunit. Mutagenesis of a cSH2 contact residue activates downstream signaling in cells. This inhibitory contact ties up the C-terminal region of the p110? catalytic subunit, which is essential for lipid kinase activity. In vitro, p110? basal activity is tightly restrained by contacts with three p85 domains: the cSH2, nSH2, and iSH2. RTK phosphopeptides relieve inhibition by nSH2 and cSH2 using completely different mechanisms. The binding site for the RTK's pYXXM motif is exposed on the cSH2, requiring an extended RTK motif to reach and disrupt the inhibitory contact with p110?. This contrasts with the nSH2 where the pY-binding site itself forms the inhibitory contact. This establishes an unusual mechanism by which p85 SH2 domains contribute to RTK signaling specificities.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1097-4164
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
567-78
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structure of lipid kinase p110?/p85? elucidates an unusual SH2-domain-mediated inhibitory mechanism.
pubmed:affiliation
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't