FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase

Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical...

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Autores principales: Guan, Jikui, Umapathy, Ganesh, Yamazaki, Yasuo, Wolfstetter, Georg, Mendoza, Patricia, Pfeifer, Kathrin, Mohammed, Ateequrrahman, Hugosson, Fredrik, Zhang, Hongbing, Hsu, Amy W, Halenbeck, Robert, Hallberg, Bengt, Palmer, Ruth H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Cell Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658194/
https://www.ncbi.nlm.nih.gov/pubmed/26418745
http://dx.doi.org/10.7554/eLife.09811
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author Guan, Jikui
Umapathy, Ganesh
Yamazaki, Yasuo
Wolfstetter, Georg
Mendoza, Patricia
Pfeifer, Kathrin
Mohammed, Ateequrrahman
Hugosson, Fredrik
Zhang, Hongbing
Hsu, Amy W
Halenbeck, Robert
Hallberg, Bengt
Palmer, Ruth H
author_facet Guan, Jikui
Umapathy, Ganesh
Yamazaki, Yasuo
Wolfstetter, Georg
Mendoza, Patricia
Pfeifer, Kathrin
Mohammed, Ateequrrahman
Hugosson, Fredrik
Zhang, Hongbing
Hsu, Amy W
Halenbeck, Robert
Hallberg, Bengt
Palmer, Ruth H
author_sort Guan, Jikui
collection PubMed
description Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild-type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor. DOI: http://dx.doi.org/10.7554/eLife.09811.001
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spelling pubmed-46581942015-11-25 FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase Guan, Jikui Umapathy, Ganesh Yamazaki, Yasuo Wolfstetter, Georg Mendoza, Patricia Pfeifer, Kathrin Mohammed, Ateequrrahman Hugosson, Fredrik Zhang, Hongbing Hsu, Amy W Halenbeck, Robert Hallberg, Bengt Palmer, Ruth H eLife Cell Biology Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild-type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor. DOI: http://dx.doi.org/10.7554/eLife.09811.001 eLife Sciences Publications, Ltd 2015-09-29 /pmc/articles/PMC4658194/ /pubmed/26418745 http://dx.doi.org/10.7554/eLife.09811 Text en © 2015, Guan et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Guan, Jikui
Umapathy, Ganesh
Yamazaki, Yasuo
Wolfstetter, Georg
Mendoza, Patricia
Pfeifer, Kathrin
Mohammed, Ateequrrahman
Hugosson, Fredrik
Zhang, Hongbing
Hsu, Amy W
Halenbeck, Robert
Hallberg, Bengt
Palmer, Ruth H
FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
title FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
title_full FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
title_fullStr FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
title_full_unstemmed FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
title_short FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
title_sort fam150a and fam150b are activating ligands for anaplastic lymphoma kinase
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658194/
https://www.ncbi.nlm.nih.gov/pubmed/26418745
http://dx.doi.org/10.7554/eLife.09811
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