FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2007886374> ?p ?o ?g. }

• W2007886374 endingPage "16123" @default.
• W2007886374 startingPage "16115" @default.
• W2007886374 abstract "Low density lipoprotein receptor-related protein 6 (LRP6) and its homologue LRP5 serve as Wnt co-receptors that are essential for the Wnt/beta-catenin pathway. Wnt activation of LRP6 leads to recruitment of the scaffolding protein Axin and inhibition of Axin-mediated phosphorylation/destruction of beta-catenin. We showed that five conserved PPPSP motifs in the LRP6 intracellular domain are required for LRP6 function, and mutation of these motifs together abolishes LRP6 signaling activity. We further showed that Wnt induces the phosphorylation of a prototypic PPPSP motif, which provides a docking site for Axin and is sufficient to transfer signaling activity to a heterologous receptor. However, the activity, regulation, and functionality of multiple PPPSP motifs in LRP6 have not been characterized. Here we provide a comprehensive analysis of all five PPPSP motifs in LRP6. We define the core amino acid residues of a prototypic PPPSP motif via alanine scanning mutagenesis and demonstrate that each of the five PPPSP motifs exhibits signaling and Axin binding activity in isolation. We generated two novel phosphorylation-specific antibodies to additional PPPSP motifs and show that Wnt induces phosphorylation of these motifs in the endogenous LRP6 through glycogen synthase kinase 3. Finally, we uncover the critical cooperativity of PPPSP motifs in the full-length LRP6 by demonstrating that LRP6 mutants lacking a single PPPSP motif display compromised function, whereas LRP6 mutants lacking two of the five PPPSP motifs are mostly inactive. This cooperativity appears to reflect the ability of PPPSP motifs to promote the phosphorylation of one another and to interact with Axin synergistically. These results establish the critical role and a common phosphorylation/activation mechanism for the PPPSP motifs in LRP6 and suggest that the conserved multiplicity and cooperativity of the PPPSP motifs represents a built-in amplifier for Wnt signaling by the LRP6 family of receptors." @default.
• W2007886374 created "2016-06-24" @default.
• W2007886374 creator A5000021060 @default.
• W2007886374 creator A5024947584 @default.
• W2007886374 creator A5026954724 @default.
• W2007886374 creator A5057482622 @default.
• W2007886374 creator A5086071420 @default.
• W2007886374 date "2008-06-01" @default.
• W2007886374 modified "2023-09-27" @default.
• W2007886374 title "Wnt Signal Amplification via Activity, Cooperativity, and Regulation of Multiple Intracellular PPPSP Motifs in the Wnt Co-receptor LRP6" @default.
• W2007886374 cites W1635607892 @default.
• W2007886374 cites W1997935003 @default.
• W2007886374 cites W2002073678 @default.
• W2007886374 cites W2008221746 @default.
• W2007886374 cites W2010217881 @default.
• W2007886374 cites W2033149299 @default.
• W2007886374 cites W2035809306 @default.
• W2007886374 cites W2040942754 @default.
• W2007886374 cites W2046813157 @default.
• W2007886374 cites W2050839067 @default.
• W2007886374 cites W2051907575 @default.
• W2007886374 cites W2065431388 @default.
• W2007886374 cites W2086694435 @default.
• W2007886374 cites W2091258025 @default.
• W2007886374 cites W2107648723 @default.
• W2007886374 cites W2111113377 @default.
• W2007886374 cites W2119413986 @default.
• W2007886374 cites W2152769008 @default.
• W2007886374 cites W2155308439 @default.
• W2007886374 cites W2352023541 @default.
• W2007886374 cites W4256264762 @default.
• W2007886374 cites W4321061121 @default.
• W2007886374 doi "https://doi.org/10.1074/jbc.m800327200" @default.
• W2007886374 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2414294" @default.
• W2007886374 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18362152" @default.
• W2007886374 hasPublicationYear "2008" @default.
• W2007886374 type Work @default.
• W2007886374 sameAs 2007886374 @default.
• W2007886374 citedByCount "95" @default.
• W2007886374 countsByYear W20078863742012 @default.
• W2007886374 countsByYear W20078863742013 @default.
• W2007886374 countsByYear W20078863742014 @default.
• W2007886374 countsByYear W20078863742015 @default.
• W2007886374 countsByYear W20078863742016 @default.
• W2007886374 countsByYear W20078863742017 @default.
• W2007886374 countsByYear W20078863742018 @default.
• W2007886374 countsByYear W20078863742019 @default.
• W2007886374 countsByYear W20078863742020 @default.
• W2007886374 countsByYear W20078863742021 @default.
• W2007886374 countsByYear W20078863742022 @default.
• W2007886374 countsByYear W20078863742023 @default.
• W2007886374 crossrefType "journal-article" @default.
• W2007886374 hasAuthorship W2007886374A5000021060 @default.
• W2007886374 hasAuthorship W2007886374A5024947584 @default.
• W2007886374 hasAuthorship W2007886374A5026954724 @default.
• W2007886374 hasAuthorship W2007886374A5057482622 @default.
• W2007886374 hasAuthorship W2007886374A5086071420 @default.
• W2007886374 hasBestOaLocation W20078863741 @default.
• W2007886374 hasConcept C104317684 @default.
• W2007886374 hasConcept C11960822 @default.
• W2007886374 hasConcept C137620995 @default.
• W2007886374 hasConcept C143065580 @default.
• W2007886374 hasConcept C153911025 @default.
• W2007886374 hasConcept C166014724 @default.
• W2007886374 hasConcept C170320316 @default.
• W2007886374 hasConcept C182819311 @default.
• W2007886374 hasConcept C2779324961 @default.
• W2007886374 hasConcept C55493867 @default.
• W2007886374 hasConcept C62478195 @default.
• W2007886374 hasConcept C86803240 @default.
• W2007886374 hasConcept C95444343 @default.
• W2007886374 hasConceptScore W2007886374C104317684 @default.
• W2007886374 hasConceptScore W2007886374C11960822 @default.
• W2007886374 hasConceptScore W2007886374C137620995 @default.
• W2007886374 hasConceptScore W2007886374C143065580 @default.
• W2007886374 hasConceptScore W2007886374C153911025 @default.
• W2007886374 hasConceptScore W2007886374C166014724 @default.
• W2007886374 hasConceptScore W2007886374C170320316 @default.
• W2007886374 hasConceptScore W2007886374C182819311 @default.
• W2007886374 hasConceptScore W2007886374C2779324961 @default.
• W2007886374 hasConceptScore W2007886374C55493867 @default.
• W2007886374 hasConceptScore W2007886374C62478195 @default.
• W2007886374 hasConceptScore W2007886374C86803240 @default.
• W2007886374 hasConceptScore W2007886374C95444343 @default.
• W2007886374 hasIssue "23" @default.
• W2007886374 hasLocation W20078863741 @default.
• W2007886374 hasLocation W20078863742 @default.
• W2007886374 hasLocation W20078863743 @default.
• W2007886374 hasLocation W20078863744 @default.
• W2007886374 hasOpenAccess W2007886374 @default.
• W2007886374 hasPrimaryLocation W20078863741 @default.
• W2007886374 hasRelatedWork W1527340722 @default.
• W2007886374 hasRelatedWork W2060954315 @default.
• W2007886374 hasRelatedWork W2097268699 @default.
• W2007886374 hasRelatedWork W2132104888 @default.
• W2007886374 hasRelatedWork W2155769759 @default.
• W2007886374 hasRelatedWork W2398022422 @default.
• W2007886374 hasRelatedWork W2998328045 @default.

• next