How TRPM6 and TRPM7 Kinases are Regulated by Autophosphorylation
Author Information
Author(s): Clark Kristopher, Middelbeek Jeroen, Morrice Nick A., Figdor Carl G., Lasonder Edwin, van Leeuwen Frank N.
Primary Institution: Radboud University Nijmegen Medical Centre
Hypothesis
Massive autophosphorylation of the Ser/Thr-rich domain controls the protein kinase activity of TRPM6 and TRPM7.
Conclusion
The study shows that autophosphorylation of the Ser/Thr-rich domain in TRPM6 and TRPM7 enhances their ability to phosphorylate substrates.
Supporting Evidence
- TRPM6 and TRPM7 are the only two proteins in mammals with a TRP channel fused to a kinase domain.
- Autophosphorylation of TRPM7 was found to be rapid and significant, incorporating 32±4 mol of phosphate per mol of kinase.
- Deletion of the Ser/Thr-rich domain in TRPM7 significantly reduced its ability to phosphorylate substrates.
- TRPM6 also undergoes autophosphorylation in a similar manner to TRPM7, despite low sequence conservation.
Takeaway
TRPM6 and TRPM7 are proteins that help cells manage magnesium. They get better at doing their job when they add lots of phosphate groups to a special part of themselves.
Methodology
The study involved in vitro kinase assays to analyze the autophosphorylation of TRPM6 and TRPM7 and their effects on substrate phosphorylation.
Limitations
The study does not explore the direct interactions between hyperphosphorylated TRPM7 and its substrates due to experimental conditions.
Digital Object Identifier (DOI)
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