FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2045867494> ?p ?o ?g. }

• W2045867494 endingPage "19801" @default.
• W2045867494 startingPage "19796" @default.
• W2045867494 abstract "Cleavage and release (shedding) of membrane proteins is a critical regulatory step in many normal and pathological processes. Evidence suggests that the antiaging transmembrane protein Klotho (KL) is shed from the cell surface by proteolytic cleavage. In this study, we attempted to identify the enzymes responsible for the shedding of KL by treating KL-transfected COS-7 cells with a panel of proteinase inhibitors and measuring cleavage products by Western blot. We report that metalloproteinase inhibitors, including EDTA, EGTA, and TAPI-1, inhibit the shedding of KL, whereas insulin increases shedding. The effects of the inhibitors in KL-transfected COS-7 cells were repeated in studies on rat kidney slices ex vivo, which validates the use of COS-7 cells as our model system. Tissue inhibitor of metalloproteinase (Timp)-3 effectively inhibits KL cleavage, whereas Timp-1 and Timp-2 do not, a profile that indicates the involvement of members of the A Desintegrin and Metalloproteinase (ADAM) family. Cotransfection of KL with either ADAM10 or ADAM17 enhances KL cleavage, whereas cotransfection of KL with small interference RNAs specific to ADAM10 and ADAM17 inhibits KL secretion. These results indicate that KL shedding is mediated mainly by ADAM10 and ADAM17 in KL-transfected COS-7 cells. The effect of insulin is abolished when ADAM10 or ADAM17 are silenced. Furthermore, we demonstrate that the effect of insulin on KL shedding is inhibited by wortmannin, showing that insulin acts through a PI3K-dependent pathway. Insulin enhances KL shedding without increasing ADAM10 and ADAM17 mRNA and protein levels, suggesting that it acts by stimulating their proteolytic activities." @default.
• W2045867494 created "2016-06-24" @default.
• W2045867494 creator A5012268693 @default.
• W2045867494 creator A5017772141 @default.
• W2045867494 creator A5052419811 @default.
• W2045867494 creator A5053523675 @default.
• W2045867494 creator A5090770710 @default.
• W2045867494 date "2007-12-11" @default.
• W2045867494 modified "2023-10-16" @default.
• W2045867494 title "Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17" @default.
• W2045867494 cites W143011653 @default.
• W2045867494 cites W1874453010 @default.
• W2045867494 cites W1975587036 @default.
• W2045867494 cites W1983527841 @default.
• W2045867494 cites W2008285804 @default.
• W2045867494 cites W2012816457 @default.
• W2045867494 cites W2018697172 @default.
• W2045867494 cites W2019500453 @default.
• W2045867494 cites W2022114463 @default.
• W2045867494 cites W2034546193 @default.
• W2045867494 cites W2047671583 @default.
• W2045867494 cites W2049229440 @default.
• W2045867494 cites W2051567146 @default.
• W2045867494 cites W2057242511 @default.
• W2045867494 cites W2057365364 @default.
• W2045867494 cites W2100899036 @default.
• W2045867494 cites W2103550756 @default.
• W2045867494 cites W2114360920 @default.
• W2045867494 cites W2119445810 @default.
• W2045867494 cites W2132287671 @default.
• W2045867494 cites W2137720344 @default.
• W2045867494 cites W2145837099 @default.
• W2045867494 cites W4240866326 @default.
• W2045867494 doi "https://doi.org/10.1073/pnas.0709805104" @default.
• W2045867494 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2148378" @default.
• W2045867494 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18056631" @default.
• W2045867494 hasPublicationYear "2007" @default.
• W2045867494 type Work @default.
• W2045867494 sameAs 2045867494 @default.
• W2045867494 citedByCount "460" @default.
• W2045867494 countsByYear W20458674942012 @default.
• W2045867494 countsByYear W20458674942013 @default.
• W2045867494 countsByYear W20458674942014 @default.
• W2045867494 countsByYear W20458674942015 @default.
• W2045867494 countsByYear W20458674942016 @default.
• W2045867494 countsByYear W20458674942017 @default.
• W2045867494 countsByYear W20458674942018 @default.
• W2045867494 countsByYear W20458674942019 @default.
• W2045867494 countsByYear W20458674942020 @default.
• W2045867494 countsByYear W20458674942021 @default.
• W2045867494 countsByYear W20458674942022 @default.
• W2045867494 countsByYear W20458674942023 @default.
• W2045867494 crossrefType "journal-article" @default.
• W2045867494 hasAuthorship W2045867494A5012268693 @default.
• W2045867494 hasAuthorship W2045867494A5017772141 @default.
• W2045867494 hasAuthorship W2045867494A5052419811 @default.
• W2045867494 hasAuthorship W2045867494A5053523675 @default.
• W2045867494 hasAuthorship W2045867494A5090770710 @default.
• W2045867494 hasBestOaLocation W20458674941 @default.
• W2045867494 hasConcept C104317684 @default.
• W2045867494 hasConcept C109523444 @default.
• W2045867494 hasConcept C119062480 @default.
• W2045867494 hasConcept C1491633281 @default.
• W2045867494 hasConcept C151730666 @default.
• W2045867494 hasConcept C153911025 @default.
• W2045867494 hasConcept C175156509 @default.
• W2045867494 hasConcept C185592680 @default.
• W2045867494 hasConcept C2776415932 @default.
• W2045867494 hasConcept C2778259572 @default.
• W2045867494 hasConcept C2778715156 @default.
• W2045867494 hasConcept C2781373781 @default.
• W2045867494 hasConcept C28406088 @default.
• W2045867494 hasConcept C43369102 @default.
• W2045867494 hasConcept C49039625 @default.
• W2045867494 hasConcept C54009773 @default.
• W2045867494 hasConcept C55493867 @default.
• W2045867494 hasConcept C55728118 @default.
• W2045867494 hasConcept C86803240 @default.
• W2045867494 hasConcept C95444343 @default.
• W2045867494 hasConceptScore W2045867494C104317684 @default.
• W2045867494 hasConceptScore W2045867494C109523444 @default.
• W2045867494 hasConceptScore W2045867494C119062480 @default.
• W2045867494 hasConceptScore W2045867494C1491633281 @default.
• W2045867494 hasConceptScore W2045867494C151730666 @default.
• W2045867494 hasConceptScore W2045867494C153911025 @default.
• W2045867494 hasConceptScore W2045867494C175156509 @default.
• W2045867494 hasConceptScore W2045867494C185592680 @default.
• W2045867494 hasConceptScore W2045867494C2776415932 @default.
• W2045867494 hasConceptScore W2045867494C2778259572 @default.
• W2045867494 hasConceptScore W2045867494C2778715156 @default.
• W2045867494 hasConceptScore W2045867494C2781373781 @default.
• W2045867494 hasConceptScore W2045867494C28406088 @default.
• W2045867494 hasConceptScore W2045867494C43369102 @default.
• W2045867494 hasConceptScore W2045867494C49039625 @default.
• W2045867494 hasConceptScore W2045867494C54009773 @default.
• W2045867494 hasConceptScore W2045867494C55493867 @default.
• W2045867494 hasConceptScore W2045867494C55728118 @default.
• W2045867494 hasConceptScore W2045867494C86803240 @default.

• next