PMID: 28428613 RLIMS-P 1 Check other iTextMine results Issue Report
Title
| 1. | Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop. |
Abstract
| 2. | Protein kinases are essential molecules in life and their crucial function requires tight regulation. |
| 3. | Many kinases are regulated via phosphorylation within their activation loop. |
| 4. | This loop is embedded in the activation segment, which additionally contains the Mg2+ binding loop and a P + 1 loop that is important in substrate binding. |
| 5. | In this report, we identify Abl-mediated phosphorylation of a highly conserved Tyr residue in the P + 1 loop of protein kinase D2 (PKD2) during oxidative stress. |
| 6. | Remarkably, we observed that the three human PKD isoforms display very different degrees of P + 1 loop Tyr phosphorylation and we identify one of the molecular determinants for this divergence. |
| 7. | This is paralleled by a different activation mechanism of PKD1 and PKD2 during oxidative stress. |
| 8. | Tyr phosphorylation in the P + 1 loop of PKD2 increases turnover for Syntide-2, while substrate specificity and the role of PKD2 in NF-κB signaling remain unaffected. |
| 9. | Importantly, Tyr to Phe substitution renders the kinase inactive, jeopardizing its use as a non-phosphorylatable mutant. |
| 10. | Since large-scale proteomics studies identified P + 1 loop Tyr phosphorylation in more than 70 Ser/Thr kinases in multiple conditions, our results do not only demonstrate differential regulation/function of PKD isoforms under oxidative stress, but also have implications for kinase regulation in general. |
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Legend: SUBSTRATE KINASE INTERACTANT SITE GENE MIRNA ANOMALY EXPRESSION DISEASE OUTCOME/RESPONSE SR_DRUG DRUG CELL TRIGGER Normalized
Tool: RLIMS-P
| PTM enzyme | Substrate | Site | Sentence |
|---|---|---|---|
| PKD isoforms | Tyr | 1, 5 |