Regions of the JAK2 Tyrosine Kinase Required for Coupling to the Growth Hormone Receptor
| Autor: | Ikuya Sakai, Jeffrey F. Goldsmith, Woelsung Yi, Stuart J. Frank, G Gilliland, Jing Jiang, Yanming Zhao, Andrew S. Kraft |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Transcriptional Activation
Recombinant Fusion Proteins Molecular Sequence Data Growth hormone receptor Biochemistry Cell Line Epitopes Mice Transactivation Proto-Oncogene Proteins hemic and lymphatic diseases Animals Amino Acid Sequence Luciferases Molecular Biology Janus kinase 2 biology Genes fos Receptors Somatotropin Cell Biology Janus Kinase 2 Protein-Tyrosine Kinases Precipitin Tests Cell biology Transmembrane domain Protein kinase domain Mutation Cancer research biology.protein Cyclin-dependent kinase 9 Signal transduction Tyrosine kinase hormones hormone substitutes and hormone antagonists Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 270:14776-14785 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.270.24.14776 |
| Popis: | Growth hormone (GH) treatment of cells promotes activation of JAK2, a GH receptor (GHR)-associated tyrosine kinase. We now explore JAK2 regions required for GHR-induced signaling. Wild-type (WT) JAK2 and JAK2 molecules with deletions of the amino terminus (JAK2ATD), carboxyl terminus (JAK2CTD), or kinase-like domain (JAK2PKD) were each transiently coexpressed in COS-7 cells with the rabbit GHR. The following responses were assayed: GH-induced transactivation of a luciferase reporter governed by a c-fos enhancer element; GH-induced shift in the molecular mass of a cotransfected epitope-tagged extracellular signal-regulated kinase molecule; and GH-induced antiphosphotyrosine immunoprecipitability of the transfected JAK2 form. In each assay, WTJAK2 and JAK2PKD allowed GH-induced signaling, whereas JAK2ATD and JAK2CTD did not. Anti-GHR serum coimmunoprecipitated WTJAK2, JAK2PKD, and JAK2CTD, but not JAK2ATD. Finally, a chimera in which the JAK2 kinase domain replaced the GHR cytoplasmic domain signaled GH-induced transactivation. We conclude: 1) kinase-like domain deletion eliminates neither physical nor functional interaction between JAK2 and the GHR; 2) kinase domain deletion eliminates functional but not physical coupling of JAK2 to the GHR; 3) interaction with the GHR appears dependent on the NH2-terminal one-fifth of JAK2; and 4) a GH-responsive signaling unit can include as little as the GHR external and transmembrane domains and the JAK2 kinase domain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|