FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase

Elife. 2015 Sep 29;4:e09811. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Cell Line
  • Cytokines / metabolism*
  • Enzyme Activation*
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Sequence Analysis, DNA

Substances

  • ALKAL1 protein, human
  • ALKAL2 protein, human
  • Cytokines
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.