Matches in SemOpenAlex for { <https://semopenalex.org/work/W3145325535> ?p ?o ?g. }
- W3145325535 endingPage "743" @default.
- W3145325535 startingPage "733" @default.
- W3145325535 abstract "The platelet C-type lectin-like receptor CLEC-2 drives inflammation-driven venous thrombosis in mouse models of thrombo-inflammatory disease with a minimal effect on hemostasis identifying it as a target for a new class of antiplatelet agent. Here, we discuss how the protein structure and dynamic arrangement of CLEC-2 on the platelet membrane helps the receptor, which has a single YxxL motif (known as a hemITAM), to trigger intracellular signaling. CLEC-2 exists as a monomer and homo-dimer within resting platelets and forms higher-order oligomers following ligand activation, a process that is mediated by the multivalent nature of its ligands and the binding of the tandem SH2 domains of Syk to the phosphorylated hemITAM and concomitantly to PIP2 or PIP3 to localize it to the membrane. We propose that a low level of active Syk is present at the membrane in resting platelets due to phosphorylation by Src family kinases and that clustering of receptors disturbs the equilibrium between kinases and phosphatases, triggering phosphorylation of the CLEC-2 hemITAM and recruitment of Syk. Knowledge of the structure of CLEC-2 and the mechanism of platelet activation has important implications for development of therapeutics." @default.
- W3145325535 created "2021-04-13" @default.
- W3145325535 creator A5029201114 @default.
- W3145325535 creator A5037195805 @default.
- W3145325535 creator A5046557008 @default.
- W3145325535 creator A5061141800 @default.
- W3145325535 creator A5075042066 @default.
- W3145325535 creator A5082405007 @default.
- W3145325535 date "2021-04-05" @default.
- W3145325535 modified "2023-10-15" @default.
- W3145325535 title "The structure of CLEC-2: mechanisms of dimerization and higher-order clustering" @default.
- W3145325535 cites W1964216939 @default.
- W3145325535 cites W1971124929 @default.
- W3145325535 cites W1978489538 @default.
- W3145325535 cites W1979789359 @default.
- W3145325535 cites W1990313926 @default.
- W3145325535 cites W1996680212 @default.
- W3145325535 cites W2002696213 @default.
- W3145325535 cites W2002967422 @default.
- W3145325535 cites W2004755955 @default.
- W3145325535 cites W2009726341 @default.
- W3145325535 cites W2010980655 @default.
- W3145325535 cites W2013493530 @default.
- W3145325535 cites W2017888244 @default.
- W3145325535 cites W2019611548 @default.
- W3145325535 cites W2021046570 @default.
- W3145325535 cites W2030732106 @default.
- W3145325535 cites W2033001098 @default.
- W3145325535 cites W2038336599 @default.
- W3145325535 cites W2038802091 @default.
- W3145325535 cites W2049595552 @default.
- W3145325535 cites W2071549499 @default.
- W3145325535 cites W2072691337 @default.
- W3145325535 cites W2077447838 @default.
- W3145325535 cites W2077584046 @default.
- W3145325535 cites W2078045806 @default.
- W3145325535 cites W2087437295 @default.
- W3145325535 cites W2088687546 @default.
- W3145325535 cites W2090642301 @default.
- W3145325535 cites W2095331504 @default.
- W3145325535 cites W2098875129 @default.
- W3145325535 cites W2100387226 @default.
- W3145325535 cites W2107255498 @default.
- W3145325535 cites W2113255390 @default.
- W3145325535 cites W2114056096 @default.
- W3145325535 cites W2116072433 @default.
- W3145325535 cites W2117583396 @default.
- W3145325535 cites W2120391794 @default.
- W3145325535 cites W2134462640 @default.
- W3145325535 cites W2139710931 @default.
- W3145325535 cites W2148583422 @default.
- W3145325535 cites W2157095212 @default.
- W3145325535 cites W2207725031 @default.
- W3145325535 cites W2311060264 @default.
- W3145325535 cites W2561202332 @default.
- W3145325535 cites W2561967870 @default.
- W3145325535 cites W2578853149 @default.
- W3145325535 cites W2742643833 @default.
- W3145325535 cites W2750385556 @default.
- W3145325535 cites W2793062143 @default.
- W3145325535 cites W2890370625 @default.
- W3145325535 cites W2891208523 @default.
- W3145325535 cites W2907399917 @default.
- W3145325535 cites W2913310538 @default.
- W3145325535 cites W2914161826 @default.
- W3145325535 cites W2981036457 @default.
- W3145325535 cites W2986491007 @default.
- W3145325535 cites W2998573579 @default.
- W3145325535 cites W3000362980 @default.
- W3145325535 cites W3018985394 @default.
- W3145325535 cites W4210981489 @default.
- W3145325535 doi "https://doi.org/10.1080/09537104.2021.1906407" @default.
- W3145325535 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33819136" @default.
- W3145325535 hasPublicationYear "2021" @default.
- W3145325535 type Work @default.
- W3145325535 sameAs 3145325535 @default.
- W3145325535 citedByCount "14" @default.
- W3145325535 countsByYear W31453255352021 @default.
- W3145325535 countsByYear W31453255352022 @default.
- W3145325535 countsByYear W31453255352023 @default.
- W3145325535 crossrefType "journal-article" @default.
- W3145325535 hasAuthorship W3145325535A5029201114 @default.
- W3145325535 hasAuthorship W3145325535A5037195805 @default.
- W3145325535 hasAuthorship W3145325535A5046557008 @default.
- W3145325535 hasAuthorship W3145325535A5061141800 @default.
- W3145325535 hasAuthorship W3145325535A5075042066 @default.
- W3145325535 hasAuthorship W3145325535A5082405007 @default.
- W3145325535 hasConcept C11960822 @default.
- W3145325535 hasConcept C12554922 @default.
- W3145325535 hasConcept C170493617 @default.
- W3145325535 hasConcept C184235292 @default.
- W3145325535 hasConcept C185592680 @default.
- W3145325535 hasConcept C203014093 @default.
- W3145325535 hasConcept C3018697912 @default.
- W3145325535 hasConcept C35174551 @default.
- W3145325535 hasConcept C42362537 @default.
- W3145325535 hasConcept C55493867 @default.
- W3145325535 hasConcept C79879829 @default.