2. Academic Validation
  3. FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase

FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase

  • Elife. 2015 Sep 29;4:e09811. doi: 10.7554/eLife.09811.
Jikui Guan 1,  Ganesh Umapathy 1,  Yasuo Yamazaki 1,  Georg Wolfstetter 1,  Patricia Mendoza 1,  Kathrin Pfeifer 1,  Ateequrrahman Mohammed 1,  Fredrik Hugosson 1,  Hongbing Zhang 2,  Amy W Hsu 2,  Robert Halenbeck 2,  Bengt Hallberg 1,  Ruth H Palmer 1
Affiliations

Affiliations

  • 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.
PMID: 26418745 DOI: 10.7554/eLife.09811
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.

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