Pub. Date : 2015 Apr 14
PMID : 25825724
7 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | JH2 of JAK1, JAK2, and TYK2 all bind ATP, but the significance of this is unclear. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |
| 2 | Disruption of JH2 ATP binding in wild-type JAK2 has only minor effects, and in the presence of type I cytokine receptors, the mutations do not affect JAK2 activation. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |
| 3 | However, JH2 mutants devoid of ATP binding ameliorate the hyperactivation of JAK2 V617F. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |
| 4 | Disrupting ATP binding in JH2 also inhibits the hyperactivity of other pathogenic JAK2 mutants, as well as of JAK1 V658F, and prevents induction of erythrocytosis in a JAK2 V617F myeloproliferative neoplasm mouse model. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |
| 5 | Molecular dynamic simulations and thermal-shift analysis indicate that ATP binding stabilizes JH2, with a pronounced effect on the C helix region, which plays a critical role in pathogenic activation of JAK2. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |
| 6 | Taken together, our results suggest that ATP binding to JH2 serves a structural role in JAKs, which is required for aberrant activity of pathogenic JAK mutants. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |
| 7 | The inhibitory effect of abrogating JH2 ATP binding in pathogenic JAK mutants may warrant novel therapeutic approaches. | Adenosine Triphosphate | immunoglobulin heavy variable 1-53 | Mus musculus |