Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome
| Autor: | Kevin Hestir, Amy W. Hsu, Hongbing Zhang, Aileen Zhou, Elizabeth Bosch, W. Michael Kavanaugh, Brian Wong, Lewis T. Williams, Lily Pao, Ernestine Lee, Gang Wang, Haixia Liu, Thomas L. Bray, Robert Halenbeck, Arthur Brace |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Orphan receptor
Male Proteomics Multidisciplinary biology Proteome Receptor Protein-Tyrosine Kinases Biological Sciences Receptor tyrosine kinase Neuron-derived orphan receptor 1 Cell biology Protein Structure Tertiary HEK293 Cells Cell surface receptor ROR1 biology.protein Cytokines Humans Female Signal transduction Phosphorylation Platelet-derived growth factor receptor G protein-coupled receptor Protein Binding Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 111(44) |
| ISSN: | 1091-6490 |
| Popis: | There are many transmembrane receptor-like proteins whose ligands have not been identified. A strategy for finding ligands when little is known about their tissue source is to screen each extracellular protein individually expressed in an array format by using a sensitive functional readout. Taking this approach, we have screened a large collection (3,191 proteins) of extracellular proteins for their ability to activate signaling of an orphan receptor, leukocyte tyrosine kinase (LTK). Only two related secreted factors, FAM150A and FAM150B (family with sequence similarity 150 member A and member B), stimulated LTK phosphorylation. FAM150A binds LTK extracellular domain with high affinity ( K D = 28 pM). FAM150A stimulates LTK phosphorylation in a ligand-dependent manner. This strategy provides an efficient approach for identifying functional ligands for other orphan receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|