PKB-Mediated Thr649 Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25923736.
- Also identified by DOI 10.1371/journal.pone.0124491 and PMC identifier 4414484.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The Rab GTPase activating protein (RabGAP), AS160/TBC1D4, is an important substrate of protein kinase B (PKB), and regulates insulin-stimulated trafficking of glucose transporter 4. Besides, AS160/TBC1D4 has also been shown to regulate trafficking of many other membrane proteins including FA translocase/CD36 in cardiomyocytes. However, it is not clear whether it plays any role in regulating heart functions in vivo. Here, we found that PKB-mediated phosphorylation of Thr649 on AS160/TBC1D4 represented one of the major PAS-binding signals in the heart in response to insulin. Mutation of Thr649 to a non-phosphorylatable alanine increased the R-wave amplitude in the AS160Thr649Ala knockin mice. However, this knockin mutation did not affect the heart functions under both normal and infarct conditions. Interestingly, myocardial infarction induced the expression of a related RabGAP, TBC1D1, in the infarct zone as well as in the border zone. Together, these data show that the Thr649 phosphorylation of AS160/TBC1D4 plays an important role in the heart's electrical conduction system through regulating the R-wave amplitude.
Medical subject headings
- GTPase-Activating Proteins
- Glucose Transporter Type 4
- Heart Conduction System
- Myocardial Infarction
- Proto-Oncogene Proteins c-akt
- Threonine