FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2018204057> ?p ?o ?g. }

• W2018204057 endingPage "7697" @default.
• W2018204057 startingPage "7692" @default.
• W2018204057 abstract "ErbB3/HER3 is one of four members of the human epidermal growth factor receptor (EGFR/HER) or ErbB receptor tyrosine kinase family. ErbB3 binds neuregulins via its extracellular region and signals primarily by heterodimerizing with ErbB2/HER2/Neu. A recently appreciated role for ErbB3 in resistance of tumor cells to EGFR/ErbB2-targeted therapeutics has made it a focus of attention. However, efforts to inactivate ErbB3 therapeutically in parallel with other ErbB receptors are challenging because its intracellular kinase domain is thought to be an inactive pseudokinase that lacks several key conserved (and catalytically important) residues-including the catalytic base aspartate. We report here that, despite these sequence alterations, ErbB3 retains sufficient kinase activity to robustly trans-autophosphorylate its intracellular region--although it is substantially less active than EGFR and does not phosphorylate exogenous peptides. The ErbB3 kinase domain binds ATP with a K(d) of approximately 1.1 microM. We describe a crystal structure of ErbB3 kinase bound to an ATP analogue, which resembles the inactive EGFR and ErbB4 kinase domains (but with a shortened alphaC-helix). Whereas mutations that destabilize this configuration activate EGFR and ErbB4 (and promote EGFR-dependent lung cancers), a similar mutation conversely inactivates ErbB3. Using quantum mechanics/molecular mechanics simulations, we delineate a reaction pathway for ErbB3-catalyzed phosphoryl transfer that does not require the conserved catalytic base and can be catalyzed by the inactive-like configuration observed crystallographically. These findings suggest that ErbB3 kinase activity within receptor dimers may be crucial for signaling and could represent an important therapeutic target." @default.
• W2018204057 created "2016-06-24" @default.
• W2018204057 creator A5012147644 @default.
• W2018204057 creator A5037007496 @default.
• W2018204057 creator A5049412007 @default.
• W2018204057 creator A5073959537 @default.
• W2018204057 creator A5081040738 @default.
• W2018204057 date "2010-03-29" @default.
• W2018204057 modified "2023-09-29" @default.
• W2018204057 title "ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation" @default.
• W2018204057 cites W1514463309 @default.
• W2018204057 cites W1520077451 @default.
• W2018204057 cites W1520497557 @default.
• W2018204057 cites W1539796472 @default.
• W2018204057 cites W1835811038 @default.
• W2018204057 cites W1967394241 @default.
• W2018204057 cites W1971758334 @default.
• W2018204057 cites W1973555911 @default.
• W2018204057 cites W1978343870 @default.
• W2018204057 cites W1988588903 @default.
• W2018204057 cites W1992945955 @default.
• W2018204057 cites W1993804787 @default.
• W2018204057 cites W1995017064 @default.
• W2018204057 cites W1998971866 @default.
• W2018204057 cites W2000394780 @default.
• W2018204057 cites W2001641653 @default.
• W2018204057 cites W2007466764 @default.
• W2018204057 cites W2012915718 @default.
• W2018204057 cites W2014111401 @default.
• W2018204057 cites W2016655288 @default.
• W2018204057 cites W2017081079 @default.
• W2018204057 cites W2020257412 @default.
• W2018204057 cites W2023423199 @default.
• W2018204057 cites W2033471769 @default.
• W2018204057 cites W2040333595 @default.
• W2018204057 cites W2044075747 @default.
• W2018204057 cites W2046740077 @default.
• W2018204057 cites W2048905477 @default.
• W2018204057 cites W2050046701 @default.
• W2018204057 cites W2056184329 @default.
• W2018204057 cites W2056928595 @default.
• W2018204057 cites W2072685915 @default.
• W2018204057 cites W2086785691 @default.
• W2018204057 cites W2099203391 @default.
• W2018204057 cites W2099387330 @default.
• W2018204057 cites W2100794900 @default.
• W2018204057 cites W2106186049 @default.
• W2018204057 cites W2111109297 @default.
• W2018204057 cites W2112200653 @default.
• W2018204057 cites W2115969107 @default.
• W2018204057 cites W2133185088 @default.
• W2018204057 cites W2136367178 @default.
• W2018204057 cites W2144081223 @default.
• W2018204057 cites W2146943926 @default.
• W2018204057 cites W2254360823 @default.
• W2018204057 cites W279429461 @default.
• W2018204057 cites W4237869558 @default.
• W2018204057 doi "https://doi.org/10.1073/pnas.1002753107" @default.
• W2018204057 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2867849" @default.
• W2018204057 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20351256" @default.
• W2018204057 hasPublicationYear "2010" @default.
• W2018204057 type Work @default.
• W2018204057 sameAs 2018204057 @default.
• W2018204057 citedByCount "417" @default.
• W2018204057 countsByYear W20182040572012 @default.
• W2018204057 countsByYear W20182040572013 @default.
• W2018204057 countsByYear W20182040572014 @default.
• W2018204057 countsByYear W20182040572015 @default.
• W2018204057 countsByYear W20182040572016 @default.
• W2018204057 countsByYear W20182040572017 @default.
• W2018204057 countsByYear W20182040572018 @default.
• W2018204057 countsByYear W20182040572019 @default.
• W2018204057 countsByYear W20182040572020 @default.
• W2018204057 countsByYear W20182040572021 @default.
• W2018204057 countsByYear W20182040572022 @default.
• W2018204057 countsByYear W20182040572023 @default.
• W2018204057 crossrefType "journal-article" @default.
• W2018204057 hasAuthorship W2018204057A5012147644 @default.
• W2018204057 hasAuthorship W2018204057A5037007496 @default.
• W2018204057 hasAuthorship W2018204057A5049412007 @default.
• W2018204057 hasAuthorship W2018204057A5073959537 @default.
• W2018204057 hasAuthorship W2018204057A5081040738 @default.
• W2018204057 hasBestOaLocation W20182040571 @default.
• W2018204057 hasConcept C101544691 @default.
• W2018204057 hasConcept C104317684 @default.
• W2018204057 hasConcept C115456853 @default.
• W2018204057 hasConcept C143065580 @default.
• W2018204057 hasConcept C150109051 @default.
• W2018204057 hasConcept C184235292 @default.
• W2018204057 hasConcept C185592680 @default.
• W2018204057 hasConcept C2779251935 @default.
• W2018204057 hasConcept C2780943970 @default.
• W2018204057 hasConcept C32619005 @default.
• W2018204057 hasConcept C42362537 @default.
• W2018204057 hasConcept C55493867 @default.
• W2018204057 hasConcept C62478195 @default.
• W2018204057 hasConcept C86803240 @default.
• W2018204057 hasConcept C95444343 @default.

• next