Guan, J., Umapathy, G., Yamazaki, Y., Wolfstetter, G., Mendoza, P., Pfeifer, K., Mohammed, A., Hugosson, F., Zhang, H., Hsu, A.W., Halenbeck, R., Hallberg, B., Palmer, R.H. (2015). FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase.  eLife 4(): e09811.

FBrf0236018

Research paper

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.

PMC4658194 (PMC) (EuropePMC)