The receptor tyrosine kinase Ror2 associates with and is activated by casein kinase Iepsilon
| Autor: | Kengo Iozumi, Akira Kikuchi, Toru Takumi, Hiroaki Suzuki, Shuichi Kani, Michiru Nishita, Isao Oishi, Hiroyuki Yamamoto, Akinori Yoda, Yasuhiro Minami, Akira Nomachi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
G-Protein-Coupled Receptor Kinase 3
Casein Kinase 1 epsilon Protein tyrosine phosphatase SH2 domain Receptor Tyrosine Kinase-like Orphan Receptors Biochemistry Receptor tyrosine kinase chemistry.chemical_compound Mice Two-Hybrid System Techniques Animals Phosphorylation Molecular Biology Sequence Deletion Serine/threonine-specific protein kinase biology Base Sequence Autophosphorylation Receptor Protein-Tyrosine Kinases Tyrosine phosphorylation Cell Biology 3T3 Cells Cyclic AMP-Dependent Protein Kinases Protein Structure Tertiary body regions chemistry beta-Adrenergic Receptor Kinases ROR1 Mutation biology.protein Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | The Journal of biological chemistry. 279(48) |
| ISSN: | 0021-9258 |
| Popis: | Ror2, a member of the mammalian Ror family of receptor tyrosine kinases, plays important roles in developmental morphogenesis, although the mechanism underlying activation of Ror2 remains largely elusive. We show that when expressed in mammalian cells, Ror2 associates with casein kinase Iepsilon (CKIepsilon), a crucial regulator of Wnt signaling. This association occurs primarily via the cytoplasmic C-terminal proline-rich domain of Ror2. We also show that Ror2 is phosphorylated by CKIepsilon on serine/threonine residues, in its C-terminal serine/threonine-rich 2 domain, resulting in autophosphorylation of Ror2 on tyrosine residues. Furthermore, it was found that association of Ror2 with CKIepsilon is required for its serine/threonine phosphorylation by CKIepsilon. Site-directed mutagenesis of tyrosine residues in Ror2 reveals that the sites of phosphorylation are contained among the five tyrosine residues in the proline-rich domain but not among the four tyrosine residues in the tyrosine kinase domain. Moreover, we show that in mammalian cells, CKIepsilon-mediated phosphorylation of Ror2 on serine/threonine and tyrosine residues is followed by the tyrosine phosphorylation of G protein-coupled receptor kinase 2, a kinase with a developmental expression pattern that is remarkably similar to that of Ror2. Intriguingly, a mutant of Ror2 lacking five tyrosine residues, including the autophosphorylation sites, fails to tyrosine phosphorylate G protein-coupled receptor kinase 2. This indicates that autophosphorylation of Ror2 is required for full activation of its tyrosine kinase activity. These findings demonstrate a novel role for CKIepsilon in the regulation of Ror2 tyrosine kinase. |
| Databáze: | OpenAIRE |
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