FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2550652287> ?p ?o ?g. }

• W2550652287 abstract "Abstract Abstract 3683 Poster Board III-619 Rap1, a small GTPase of the Ras superfamily, originally identified by its ability to reverse Ras-mediated transformation, is now known to regulate cytoskeletal reorganization, cell morphology, adherens junction positioning and adhesion. The best-studied function of Rap1 is inside-out activation of integrins and cell adhesion. Two newly identified Rap1 effectors, RapL and RIAM, have been implicated in Rap1 mediated in inside-out activation of integrins and cell adhesion. However, significant differences in the structure and interactions of these molecules indicate that they may mediate distinct signaling events. RIAM has a N-terminal coiled-coil region, central RA and pleckstrin homology (PH) domains, and proline-rich N-terminal and C-terminal regions, with multiple FPPPP motifs capable of interacting with the EVH1 domains of the actin regulatory proteins Ena/VASP, multiple XPPPP motifs interacting with Profilin and multiple PXXP motifs capable of interacting with SH3 domain containing proteins. Because of these properties RIAM is a regulator of actin polymerization but also interacts with components of the T cell signaling machinery. In contrast, RapL has an RBD (Ras binding domain-structurally similar to RA domain) and a C-terminal coiled-coil region and interacts with Rap1 via its RBD domain and its N-terminal region, and with the aL subunit of LFA-1 via its C-terminal domain. In the present study we investigated the role of RIAM and RapL in regulating signaling and functional events activated via the TCR. For this purpose we used RIAM-knockdown (KD) and RapL-KD Jurkat T cells in which endogenous RIAM and RapL, respectively, had been depleted by siRNA. Whereas activation of the extracellular signal regulated kinases MEK1/2 and Erk1/2 was impaired by depletion of RIAM, activation of these kinases was unaffected by depletion of RapL. In contrast, activation of p38 was unaltered in RIAM-KD cells but was abrogated in RapL-KD cells. Moreover, RIAM knockdown resulted in impaired activation of Ras and Rap1 due to defective activation of the calcium and diacylglycerole-dependent GEFs, RasGRP1 and CalDAG-GEFI. In contrast, RapL knockdown had no effect on these events compared to control Jurkat T cells. Strikingly, RIAM-KD cells displayed impaired IL-2 production in response to stimulation with SEE-loaded APC or to TCR/CD3-plus-CD28 crosslinking, whereas RapL-KD cells displayed a dramatic increase in IL-2 production upon stimulation under the same conditions. These results indicate that although both RIAM and RapL regulate Rap1-dependent LFA-1 activation, these molecules have distinct roles in regulating signaling and functional outcomes of T cell responses after T cell receptor triggering. Disclosures: No relevant conflicts of interest to declare." @default.
• W2550652287 created "2016-11-30" @default.
• W2550652287 creator A5000671033 @default.
• W2550652287 creator A5004537586 @default.
• W2550652287 creator A5016169031 @default.
• W2550652287 date "2009-11-20" @default.
• W2550652287 modified "2023-09-30" @default.
• W2550652287 title "RIAM and RapL Regulate Distinct Signaling Events and Functional Outcomes Upon TCR-Mediated Activation." @default.
• W2550652287 doi "https://doi.org/10.1182/blood.v114.22.3683.3683" @default.
• W2550652287 hasPublicationYear "2009" @default.
• W2550652287 type Work @default.
• W2550652287 sameAs 2550652287 @default.
• W2550652287 citedByCount "0" @default.
• W2550652287 crossrefType "journal-article" @default.
• W2550652287 hasAuthorship W2550652287A5000671033 @default.
• W2550652287 hasAuthorship W2550652287A5004537586 @default.
• W2550652287 hasAuthorship W2550652287A5016169031 @default.
• W2550652287 hasConcept C125705527 @default.
• W2550652287 hasConcept C126619667 @default.
• W2550652287 hasConcept C142669718 @default.
• W2550652287 hasConcept C1491633281 @default.
• W2550652287 hasConcept C170493617 @default.
• W2550652287 hasConcept C185592680 @default.
• W2550652287 hasConcept C195687474 @default.
• W2550652287 hasConcept C207332259 @default.
• W2550652287 hasConcept C2776179587 @default.
• W2550652287 hasConcept C2993400109 @default.
• W2550652287 hasConcept C49658373 @default.
• W2550652287 hasConcept C51785407 @default.
• W2550652287 hasConcept C55493867 @default.
• W2550652287 hasConcept C62478195 @default.
• W2550652287 hasConcept C85789140 @default.
• W2550652287 hasConcept C86803240 @default.
• W2550652287 hasConcept C95444343 @default.
• W2550652287 hasConceptScore W2550652287C125705527 @default.
• W2550652287 hasConceptScore W2550652287C126619667 @default.
• W2550652287 hasConceptScore W2550652287C142669718 @default.
• W2550652287 hasConceptScore W2550652287C1491633281 @default.
• W2550652287 hasConceptScore W2550652287C170493617 @default.
• W2550652287 hasConceptScore W2550652287C185592680 @default.
• W2550652287 hasConceptScore W2550652287C195687474 @default.
• W2550652287 hasConceptScore W2550652287C207332259 @default.
• W2550652287 hasConceptScore W2550652287C2776179587 @default.
• W2550652287 hasConceptScore W2550652287C2993400109 @default.
• W2550652287 hasConceptScore W2550652287C49658373 @default.
• W2550652287 hasConceptScore W2550652287C51785407 @default.
• W2550652287 hasConceptScore W2550652287C55493867 @default.
• W2550652287 hasConceptScore W2550652287C62478195 @default.
• W2550652287 hasConceptScore W2550652287C85789140 @default.
• W2550652287 hasConceptScore W2550652287C86803240 @default.
• W2550652287 hasConceptScore W2550652287C95444343 @default.
• W2550652287 hasLocation W25506522871 @default.
• W2550652287 hasOpenAccess W2550652287 @default.
• W2550652287 hasPrimaryLocation W25506522871 @default.
• W2550652287 hasRelatedWork W117132871 @default.
• W2550652287 hasRelatedWork W1517048488 @default.
• W2550652287 hasRelatedWork W1546898491 @default.
• W2550652287 hasRelatedWork W1660818112 @default.
• W2550652287 hasRelatedWork W1964399995 @default.
• W2550652287 hasRelatedWork W1968048262 @default.
• W2550652287 hasRelatedWork W1974791474 @default.
• W2550652287 hasRelatedWork W1986168751 @default.
• W2550652287 hasRelatedWork W1993705617 @default.
• W2550652287 hasRelatedWork W2001706607 @default.
• W2550652287 hasRelatedWork W2048788153 @default.
• W2550652287 hasRelatedWork W2070166919 @default.
• W2550652287 hasRelatedWork W2096563079 @default.
• W2550652287 hasRelatedWork W2109447374 @default.
• W2550652287 hasRelatedWork W2144584955 @default.
• W2550652287 hasRelatedWork W2147095766 @default.
• W2550652287 hasRelatedWork W2150273078 @default.
• W2550652287 hasRelatedWork W2161376583 @default.
• W2550652287 hasRelatedWork W2768806884 @default.
• W2550652287 hasRelatedWork W4658854 @default.
• W2550652287 isParatext "false" @default.
• W2550652287 isRetracted "false" @default.
• W2550652287 magId "2550652287" @default.
• W2550652287 workType "article" @default.