FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2102005789> ?p ?o ?g. }

• W2102005789 endingPage "3666" @default.
• W2102005789 startingPage "3655" @default.
• W2102005789 abstract "Somatic missense mutations in PIK3CA, which encodes the p110α catalytic subunit of phosphoinositide 3-kinases, occur frequently in human cancers. Activating mutations spread across multiple domains, some of which are located at inhibitory contact sites formed with the regulatory subunit p85α. PIK3R1, which encodes p85α, also has activating somatic mutations. We find a strong correlation between lipid kinase and lipid-binding activities for both wild-type (WT) and a representative set of oncogenic mutant complexes of p110α/p85α. Lipid binding involves both electrostatic and hydrophobic interactions. Activation caused by a phosphorylated receptor tyrosine kinase (RTK) peptide binding to the p85α N-terminal SH2 domain (nSH2) induces lipid binding. This depends on the polybasic activation loop as well as a conserved hydrophobic motif in the C-terminal region of the kinase domain. The hotspot E545K mutant largely mimics the activated WT p110α. It shows the highest basal activity and lipid binding, and is not significantly activated by an RTK phosphopeptide. Both the hotspot H1047R mutant and rare mutations (C420R, M1043I, H1047L, G1049R and p85α-N564D) also show increased basal kinase activities and lipid binding. However, their activities are further enhanced by an RTK phosphopeptide to levels markedly exceeding that of activated WT p110α. Phosphopeptide binding to p110β/p85α and p110δ/p85α complexes also induces their lipid binding. We present a crystal structure of WT p110α complexed with the p85α inter-SH2 domain and the inhibitor PIK-108. Additional to the ATP-binding pocket, an unexpected, second PIK-108 binding site is observed in the kinase C-lobe. We show a global conformational change in p110α consistent with allosteric regulation of the kinase domain by nSH2. These findings broaden our understanding of the differential biological outputs exhibited by distinct types of mutations regarding growth factor dependence, and suggest a two-tier classification scheme relating p110α and p85α mutations with signalling potential." @default.
• W2102005789 created "2016-06-24" @default.
• W2102005789 creator A5022473461 @default.
• W2102005789 creator A5056575777 @default.
• W2102005789 creator A5068057658 @default.
• W2102005789 date "2011-11-28" @default.
• W2102005789 modified "2023-10-18" @default.
• W2102005789 title "Regulation of lipid binding underlies the activation mechanism of class IA PI3-kinases" @default.
• W2102005789 cites W1486786974 @default.
• W2102005789 cites W1547466369 @default.
• W2102005789 cites W1600022110 @default.
• W2102005789 cites W1968260093 @default.
• W2102005789 cites W1969292035 @default.
• W2102005789 cites W1974606305 @default.
• W2102005789 cites W1977267072 @default.
• W2102005789 cites W1978981032 @default.
• W2102005789 cites W1984621921 @default.
• W2102005789 cites W1988864736 @default.
• W2102005789 cites W1989008399 @default.
• W2102005789 cites W1991166678 @default.
• W2102005789 cites W1999226878 @default.
• W2102005789 cites W2000954296 @default.
• W2102005789 cites W2001999652 @default.
• W2102005789 cites W2006734560 @default.
• W2102005789 cites W2011360946 @default.
• W2102005789 cites W2012306540 @default.
• W2102005789 cites W2014096417 @default.
• W2102005789 cites W2019239252 @default.
• W2102005789 cites W2027361781 @default.
• W2102005789 cites W2043312574 @default.
• W2102005789 cites W2043865307 @default.
• W2102005789 cites W2046584993 @default.
• W2102005789 cites W2054607545 @default.
• W2102005789 cites W2060616543 @default.
• W2102005789 cites W2072867699 @default.
• W2102005789 cites W2085483616 @default.
• W2102005789 cites W2090038231 @default.
• W2102005789 cites W2099313880 @default.
• W2102005789 cites W2099661341 @default.
• W2102005789 cites W2109099165 @default.
• W2102005789 cites W2109799459 @default.
• W2102005789 cites W2110894800 @default.
• W2102005789 cites W2117692326 @default.
• W2102005789 cites W2120772351 @default.
• W2102005789 cites W2123777737 @default.
• W2102005789 cites W2127355894 @default.
• W2102005789 cites W2129172946 @default.
• W2102005789 cites W2132016433 @default.
• W2102005789 cites W2133054306 @default.
• W2102005789 cites W2135177611 @default.
• W2102005789 cites W2144040817 @default.
• W2102005789 cites W2146414563 @default.
• W2102005789 cites W2151258296 @default.
• W2102005789 cites W2154206349 @default.
• W2102005789 cites W2157489886 @default.
• W2102005789 cites W2164779274 @default.
• W2102005789 cites W2165992619 @default.
• W2102005789 doi "https://doi.org/10.1038/onc.2011.532" @default.
• W2102005789 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3378484" @default.
• W2102005789 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22120714" @default.
• W2102005789 hasPublicationYear "2011" @default.
• W2102005789 type Work @default.
• W2102005789 sameAs 2102005789 @default.
• W2102005789 citedByCount "92" @default.
• W2102005789 countsByYear W21020057892012 @default.
• W2102005789 countsByYear W21020057892013 @default.
• W2102005789 countsByYear W21020057892014 @default.
• W2102005789 countsByYear W21020057892015 @default.
• W2102005789 countsByYear W21020057892016 @default.
• W2102005789 countsByYear W21020057892017 @default.
• W2102005789 countsByYear W21020057892018 @default.
• W2102005789 countsByYear W21020057892019 @default.
• W2102005789 countsByYear W21020057892020 @default.
• W2102005789 countsByYear W21020057892021 @default.
• W2102005789 countsByYear W21020057892022 @default.
• W2102005789 countsByYear W21020057892023 @default.
• W2102005789 crossrefType "journal-article" @default.
• W2102005789 hasAuthorship W2102005789A5022473461 @default.
• W2102005789 hasAuthorship W2102005789A5056575777 @default.
• W2102005789 hasAuthorship W2102005789A5068057658 @default.
• W2102005789 hasBestOaLocation W21020057891 @default.
• W2102005789 hasConcept C104292427 @default.
• W2102005789 hasConcept C104317684 @default.
• W2102005789 hasConcept C107824862 @default.
• W2102005789 hasConcept C11960822 @default.
• W2102005789 hasConcept C143065580 @default.
• W2102005789 hasConcept C153911025 @default.
• W2102005789 hasConcept C184235292 @default.
• W2102005789 hasConcept C2779933727 @default.
• W2102005789 hasConcept C2780610907 @default.
• W2102005789 hasConcept C2781465904 @default.
• W2102005789 hasConcept C32619005 @default.
• W2102005789 hasConcept C51639874 @default.
• W2102005789 hasConcept C55493867 @default.
• W2102005789 hasConcept C86803240 @default.
• W2102005789 hasConcept C95444343 @default.
• W2102005789 hasConceptScore W2102005789C104292427 @default.
• W2102005789 hasConceptScore W2102005789C104317684 @default.

• next