A functional Jak2 tyrosine kinase domain is essential for mouse development
| Autor: | Kristen Frenzel, Issam McDoom, Kenneth E. Bernstein, Tiffany A. Wallace, Mario R. Capecchi, Peter P. Sayeski, Hong D. Xiao |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Molecular Sequence Data Embryonic Development Mitogen-activated protein kinase kinase Receptor tyrosine kinase Mice Proto-Oncogene Proteins hemic and lymphatic diseases Animals ASK1 Amino Acid Sequence Kinase activity Alleles Cells Cultured Mice Knockout Binding Sites Janus kinase 2 Base Sequence biology Gene Expression Regulation Developmental food and beverages Cell Biology Janus Kinase 2 Protein-Tyrosine Kinases Molecular biology Hematopoiesis Protein Structure Tertiary Phenotype biology.protein Cyclin-dependent kinase 9 Janus kinase Dimerization hormones hormone substitutes and hormone antagonists Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Experimental Cell Research. 312:2735-2744 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2006.05.004 |
| Popis: | Jak2 is a member of the Janus family of tyrosine kinases and is involved in cytokine signaling. As a part of a study to determine biological functions of Jak2, we used molecular modeling to identify W1038 as a residue that is critical for tyrosine kinase function. Mutation of W1038, in tandem with E1046, generates a dominant-negative form of the Jak2 protein. Mice that were engineered to express two copies of this dominant-negative Jak2 protein died in utero. Additionally, heterozygous mice expressing Jak2 with kinase activity that is moderately reduced when compared to wild-type activity appear phenotypically normal. Collectively, these data suggest that Jak2 kinase activity is essential for normal mammalian development. |
| Databáze: | OpenAIRE |
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