title: FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jikui
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Umapathy
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Georg
authors.initials: G
authors.lastname: Wolfstetter
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mendoza
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Pfeifer
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ateequrrahman
authors.initials: A
authors.lastname: Mohammed
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hugosson
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, United States.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, United States.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Hsu
authors.affiliation: Five Prime Therapeutics Inc., South San Francisco, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Halenbeck
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Hallberg
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ruth H
authors.identifier: http://orcid.org/0000-0002-2735-8470
authors.initials: RH
authors.lastname: Palmer
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: C000609778:ALKAL1 protein, human; C000609777:ALKAL2 protein, human; D016207:Cytokines; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Anaplastic lymphoma kinase; D. melanogaster; FAM150; LTK; cell biology; human; ligand; neuroblastoma; signaling