Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch
Kim, A. K.; Wu, H. D.; Inoue, T.
Show abstract
Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires elaborate coordination of sensing and actuation mechanisms built into a single molecule. Here, we rationally designed a molecular switch that changes its subcellular localization in response to an intended stimulus such as an activator of protein kinase A (PKA). By arranging the sequence for Kemptide in tandem, we designed a farnesylated peptide whose localization can dramatically change upon phosphorylation by PKA. After testing a different valence number of Kemptide as well as modulating the linker sequence connecting them, we identified an efficient peptide switch that exhibited dynamic translocation between plasma membranes and internal endomembranes in a PKA activity dependent manner. Due to the modular design and small size, our PKA switch can have versatile utility in future studies as a platform for visualizing and perturbing signal transduction pathways, as well as for performing synthetic operations in cells.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Allosteric inhibition of the epidermal growth factor receptor through disruption of transmembrane interactions 94%
- Optogenetic control of small GTPases reveals RhoA-mediated intracellular calcium signaling 94%
- Cholesterol promotes the formation of dimers and oligomers of the receptor tyrosine kinase ROR1 93%
Similar papers in this journal
Similar papers in this journal
- Bidirectional transfer of Engrailed homeoprotein across the plasma membrane requires PIP2 95%
- A Novel Homeostatic Mechanism Tunes PI(4,5)P2-dependent Signaling at the Plasma Membrane 94%
- Threonine phosphorylation regulates the molecular assembly and signaling of EGFR in cooperation with membrane lipids 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.