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

作者：Reshetnyak Andrey V; Murray Phillip B; Shi Xiarong; Mo Elizabeth S; Mohanty Jyotidarsini; Tome Francisco; Bai Hanwen; Gunel Murat; Lax Irit; Schlessinger Joseph^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(52): 15862-15867.

DOI：10.1073/pnas.1520099112

• cell signaling
• surface receptors
• phosphorylation
• cancer
• protein kinases

Receptor tyrosine kinases (RTKs) are a class of cell surface receptors that, upon ligand binding, stimulate a variety of critical cellular functions. The orphan receptor anaplastic lymphoma kinase (ALK) is one of very few RTKs that remain without a firmly established protein ligand. Here we present a novel cytokine, FAM150B, which we propose naming augmentor-alpha (AUG-alpha), as a ligand for ALK. AUG-alpha binds ALK with high affinity and activates ALK in cells with subnanomolar potency. Detailed binding experiments using cells expressing ALK or the related receptor leukocyte tyrosine kinase (LTK) demonstrate that AUG-alpha binds and robustly activates both ALK and LTK. We show that the previously established LTK ligand FAM150A (AUG-beta) is specific for LTK and only weakly binds to ALK. Furthermore, expression of AUG-alpha stimulates transformation of NIH/3T3 cells expressing ALK, induces IL-3 independent growth of Ba/F3 cells expressing ALK, and is expressed in neuroblastoma, a cancer partly driven by ALK. These experiments reveal the hierarchy and specificity of two cytokines as ligands for ALK and LTK and set the stage for elucidating their roles in development and disease states.

• 出版日期2015-12-29