{"database":"biostudies-other","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Josephina Sampson"],"funding":["National Research Foundation of Korea (NRF)","Cancer Research UK (CRUK)","Wellcome Trust"],"journal":["EMBO Reports"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMBOR-2021-53693V1"],"abstract":["Variants of the oncogenic EML4-ALK fusion protein contain a similar region of ALK encompassing the kinase domain, but different portions of EML4. Here we show that EML4-ALK V1 and V3 proteins form cytoplasmic foci that contain components of the MAPK, PLC and PI3K signalling pathways. The ALK inhibitors ceritinib and lorlatinib dissolve these foci and EML4-ALK V3 but not V1 protein re-localises to microtubules, an effect recapitulated in a catalytically-inactive EML4-ALK mutant. Mutations that promote a constitutively active ALK stabilise the cytoplasmic foci even in the presence of these inhibitors. In contrast, the inhibitor alectinib increases foci formation of both wild-type and catalytically-inactive EML4-ALK V3 proteins, but not a Lys-Glu salt-bridge mutant. We propose that EML4-ALK "],"repository":["biostudies-other"],"funding_grant_id":["C24461/A23302","WT104918MA","No.2020R1A2C2006815"],"pubmed_authors":["Prof. Richard Bayliss","Jene Choi","Josephina Sampson","Dr. Mark, William Richards","Dr. Andrew, M. Fry"],"additional_accession":[]},"is_claimable":false,"name":"Phase-separated foci of EML4-ALK facilitate signalling and depend upon an active kinase conformation","description":"Variants of the oncogenic EML4-ALK fusion protein contain a similar region of ALK encompassing the kinase domain, but different portions of EML4. Here we show that EML4-ALK V1 and V3 proteins form cytoplasmic foci that contain components of the MAPK, PLC and PI3K signalling pathways. The ALK inhibitors ceritinib and lorlatinib dissolve these foci and EML4-ALK V3 but not V1 protein re-localises to microtubules, an effect recapitulated in a catalytically-inactive EML4-ALK mutant. Mutations that promote a constitutively active ALK stabilise the cytoplasmic foci even in the presence of these inhibitors. In contrast, the inhibitor alectinib increases foci formation of both wild-type and catalytically-inactive EML4-ALK V3 proteins, but not a Lys-Glu salt-bridge mutant. We propose that EML4-ALK ","dates":{"release":"2022-03-01T00:00:00Z","modification":"2022-03-01T21:00:34.622Z","creation":"2022-03-01T21:00:34.622Z"},"accession":"S-SCDT-EMBOR-2021-53693V1","cross_references":{"doi":["10.15252/embr.202153693"]}}