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Elife. 2015 Sep 29;4:e09811. doi: 10.7554/eLife.09811.

FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase.

Author information

1
Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2
Five Prime Therapeutics Inc., South San Francisco, United States.

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.

KEYWORDS:

ALK; Anaplastic lymphoma kinase; D. melanogaster; FAM150; LTK; cell biology; human; ligand; neuroblastoma; signaling

PMID:
26418745
PMCID:
PMC4658194
DOI:
10.7554/eLife.09811
[Indexed for MEDLINE]
Free PMC Article

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