Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions

Many cancers (e.g., subpopulations of lung cancer, anaplastic lymphoma, and neuroblastoma) are driven by mutations in the receptor tyrosine kinase ALK (for anaplastic lymphoma kinase). However, the extracellular protein signals that regulate ALK's activity and its ligand-induced mechanism of activation remain elusive. Here we describe a cytokine designated augmentor-α that binds with high affinity and specificity to ALK's extracellular glycine-rich region, resulting in robust receptor activation. Augmentor-α also potently activates the related leukocyte tyrosine kinase (LTK) receptor, whereas a previously identified LTK ligand (augmentor-β) only weakly activates ALK. These experiments reveal an important missing link necessary for the regulation of a known oncogenic RTK, providing important insights into its biology and offering new opportunities for therapeutic intervention.