FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2470640552> ?p ?o ?g. }

• W2470640552 endingPage "17368" @default.
• W2470640552 startingPage "17360" @default.
• W2470640552 abstract "The transduction of signals generated by protein kinases and phosphatases are critical for the ability of integrin αIIbβ3 to support stable platelet adhesion and thrombus formation. Unlike kinases, it remains unclear how serine/threonine phosphatases engage the signaling networks that are initiated following integrin ligation. Because protein-protein interactions form the backbone of signal transduction, we searched for proteins that interact with the catalytic subunit of protein phosphatase 2A (PP2Ac). In a yeast two-hybrid study, we identified a novel interaction between PP2Ac and an adaptor protein CIN85 (Cbl-interacting protein of 85 kDa). Truncation and alanine mutagenesis studies revealed that PP2Ac binds to the P3 block (396PAIPPKKPRP405) of the proline-rich region in CIN85. The interaction of purified PP2Ac with CIN85 suppressed phosphatase activity. Human embryonal kidney 293 αIIbβ3 cells overexpressing a CIN85 P3 mutant, which cannot support PP2Ac binding, displayed decreased adhesion to immobilized fibrinogen. Platelets contain the ∼85 kDa CIN85 protein along with the PP2Ac-CIN85 complex. A myristylated cell-permeable peptide derived from residues 395–407 of CIN85 protein (P3 peptide) disrupted the platelet PP2Ac-CIN85 complex and decreased αIIbβ3 signaling dependent functions such as platelet spreading on fibrinogen and thrombin-mediated fibrin clot retraction. In a phospho-profiling study P3 peptide treated platelets also displayed decreased phosphorylation of several signaling proteins including Src and GSK3β. Taken together, these data support a role for the novel PP2Ac-CIN85 complex in supporting integrin-dependent platelet function by dampening the phosphatase activity. The transduction of signals generated by protein kinases and phosphatases are critical for the ability of integrin αIIbβ3 to support stable platelet adhesion and thrombus formation. Unlike kinases, it remains unclear how serine/threonine phosphatases engage the signaling networks that are initiated following integrin ligation. Because protein-protein interactions form the backbone of signal transduction, we searched for proteins that interact with the catalytic subunit of protein phosphatase 2A (PP2Ac). In a yeast two-hybrid study, we identified a novel interaction between PP2Ac and an adaptor protein CIN85 (Cbl-interacting protein of 85 kDa). Truncation and alanine mutagenesis studies revealed that PP2Ac binds to the P3 block (396PAIPPKKPRP405) of the proline-rich region in CIN85. The interaction of purified PP2Ac with CIN85 suppressed phosphatase activity. Human embryonal kidney 293 αIIbβ3 cells overexpressing a CIN85 P3 mutant, which cannot support PP2Ac binding, displayed decreased adhesion to immobilized fibrinogen. Platelets contain the ∼85 kDa CIN85 protein along with the PP2Ac-CIN85 complex. A myristylated cell-permeable peptide derived from residues 395–407 of CIN85 protein (P3 peptide) disrupted the platelet PP2Ac-CIN85 complex and decreased αIIbβ3 signaling dependent functions such as platelet spreading on fibrinogen and thrombin-mediated fibrin clot retraction. In a phospho-profiling study P3 peptide treated platelets also displayed decreased phosphorylation of several signaling proteins including Src and GSK3β. Taken together, these data support a role for the novel PP2Ac-CIN85 complex in supporting integrin-dependent platelet function by dampening the phosphatase activity." @default.
• W2470640552 created "2016-07-22" @default.
• W2470640552 creator A5005119964 @default.
• W2470640552 creator A5017039757 @default.
• W2470640552 creator A5017124801 @default.
• W2470640552 creator A5025875749 @default.
• W2470640552 creator A5026042960 @default.
• W2470640552 creator A5039588574 @default.
• W2470640552 creator A5050504925 @default.
• W2470640552 date "2016-08-01" @default.
• W2470640552 modified "2023-10-18" @default.
• W2470640552 title "A Novel Interaction of the Catalytic Subunit of Protein Phosphatase 2A with the Adaptor Protein CIN85 Suppresses Phosphatase Activity and Facilitates Platelet Outside-in αIIbβ3 Integrin Signaling" @default.
• W2470640552 cites W151043947 @default.
• W2470640552 cites W1964241796 @default.
• W2470640552 cites W1965418027 @default.
• W2470640552 cites W1966880102 @default.
• W2470640552 cites W1969162892 @default.
• W2470640552 cites W1969653234 @default.
• W2470640552 cites W1971124929 @default.
• W2470640552 cites W1974894246 @default.
• W2470640552 cites W1979438759 @default.
• W2470640552 cites W1993512412 @default.
• W2470640552 cites W1996544591 @default.
• W2470640552 cites W2003676289 @default.
• W2470640552 cites W2007533966 @default.
• W2470640552 cites W2021359328 @default.
• W2470640552 cites W2039775874 @default.
• W2470640552 cites W2039881470 @default.
• W2470640552 cites W2039954449 @default.
• W2470640552 cites W2041171080 @default.
• W2470640552 cites W2042384618 @default.
• W2470640552 cites W2046315012 @default.
• W2470640552 cites W2046737719 @default.
• W2470640552 cites W2051826520 @default.
• W2470640552 cites W2053321291 @default.
• W2470640552 cites W2060471208 @default.
• W2470640552 cites W2065159330 @default.
• W2470640552 cites W2068829311 @default.
• W2470640552 cites W2069384743 @default.
• W2470640552 cites W2077145521 @default.
• W2470640552 cites W2084352760 @default.
• W2470640552 cites W2095414565 @default.
• W2470640552 cites W2123413961 @default.
• W2470640552 cites W2146521009 @default.
• W2470640552 cites W2153843690 @default.
• W2470640552 cites W2165408960 @default.
• W2470640552 cites W2170770662 @default.
• W2470640552 cites W2171229821 @default.
• W2470640552 cites W2329864417 @default.
• W2470640552 doi "https://doi.org/10.1074/jbc.m115.704296" @default.
• W2470640552 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5016133" @default.
• W2470640552 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27334924" @default.
• W2470640552 hasPublicationYear "2016" @default.
• W2470640552 type Work @default.
• W2470640552 sameAs 2470640552 @default.
• W2470640552 citedByCount "3" @default.
• W2470640552 countsByYear W24706405522017 @default.
• W2470640552 countsByYear W24706405522019 @default.
• W2470640552 countsByYear W24706405522021 @default.
• W2470640552 crossrefType "journal-article" @default.
• W2470640552 hasAuthorship W2470640552A5005119964 @default.
• W2470640552 hasAuthorship W2470640552A5017039757 @default.
• W2470640552 hasAuthorship W2470640552A5017124801 @default.
• W2470640552 hasAuthorship W2470640552A5025875749 @default.
• W2470640552 hasAuthorship W2470640552A5026042960 @default.
• W2470640552 hasAuthorship W2470640552A5039588574 @default.
• W2470640552 hasAuthorship W2470640552A5050504925 @default.
• W2470640552 hasBestOaLocation W24706405521 @default.
• W2470640552 hasConcept C104292427 @default.
• W2470640552 hasConcept C104317684 @default.
• W2470640552 hasConcept C108636557 @default.
• W2470640552 hasConcept C11960822 @default.
• W2470640552 hasConcept C1491633281 @default.
• W2470640552 hasConcept C178666793 @default.
• W2470640552 hasConcept C183786373 @default.
• W2470640552 hasConcept C184235292 @default.
• W2470640552 hasConcept C185592680 @default.
• W2470640552 hasConcept C195687474 @default.
• W2470640552 hasConcept C2779408958 @default.
• W2470640552 hasConcept C2910542480 @default.
• W2470640552 hasConcept C389152 @default.
• W2470640552 hasConcept C55493867 @default.
• W2470640552 hasConcept C62478195 @default.
• W2470640552 hasConcept C86803240 @default.
• W2470640552 hasConcept C95444343 @default.
• W2470640552 hasConceptScore W2470640552C104292427 @default.
• W2470640552 hasConceptScore W2470640552C104317684 @default.
• W2470640552 hasConceptScore W2470640552C108636557 @default.
• W2470640552 hasConceptScore W2470640552C11960822 @default.
• W2470640552 hasConceptScore W2470640552C1491633281 @default.
• W2470640552 hasConceptScore W2470640552C178666793 @default.
• W2470640552 hasConceptScore W2470640552C183786373 @default.
• W2470640552 hasConceptScore W2470640552C184235292 @default.
• W2470640552 hasConceptScore W2470640552C185592680 @default.
• W2470640552 hasConceptScore W2470640552C195687474 @default.
• W2470640552 hasConceptScore W2470640552C2779408958 @default.
• W2470640552 hasConceptScore W2470640552C2910542480 @default.
• W2470640552 hasConceptScore W2470640552C389152 @default.

• next