Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions
| Autor: | Xiarong Shi, Murat Gunel, Joseph Schlessinger, Francisco Tome, Jyotidarsini Mohanty, Irit Lax, Hanwen Bai, Phillip B. Murray, Andrey V. Reshetnyak, Elizabeth S. Mo |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cell signaling
Receptor Protein-Tyrosine Kinases Immunoblotting Molecular Sequence Data Ligands Receptor tyrosine kinase Cell Line Mice Cell surface receptor hemic and lymphatic diseases Cell Line Tumor Commentaries Anaplastic lymphoma kinase Animals Humans Anaplastic Lymphoma Kinase Amino Acid Sequence Cell Proliferation Orphan receptor Multidisciplinary biology Sequence Homology Amino Acid Heparin Ligand (biochemistry) Molecular biology Cell biology Enzyme Activation HEK293 Cells Doxycycline biology.protein NIH 3T3 Cells Phosphorylation Cytokines Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 112(52) |
| ISSN: | 1091-6490 |
| Popis: | 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-α (AUG-α), as a ligand for ALK. AUG-α 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-α binds and robustly activates both ALK and LTK. We show that the previously established LTK ligand FAM150A (AUG-β) is specific for LTK and only weakly binds to ALK. Furthermore, expression of AUG-α 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|