Lecture will be held in English

Hosted by

Jakub Harnoš

About the lecture

New Frontiers in PKA Signaling

Although the first crystal structure of the catalytic (C) subunit of cAMP-dependent protein kinase (PKA) was solved over 30 years ago, we are still learning new things about this ubiquitous kinase that regulates so much biology. In cells the C-subunit is stored as a holoenzyme complex with inhibitory regulatory (R) subunits that are activated by cAMP, and the quaternary structures created by each of the four functionally non-redundant R-subunits are remarkably different. These holoenzymes are then localized to specific sites in the cell, typically by A Kinase Anchoring Proteins (AKAPs) that create unique cAMP signaling islands. The isoform diversity of the C-subunit is also critical for mediating cell-specific signaling. While the well-studied Ca subunit serves as a prototype for the protein kinase superfamily, the Cb isoforms have been largely ignored although they account for nearly 50% of PKA signaling in brain. In parallel with our structural studies of PKA subunits and full-length holoenzymes, it is essential to demonstrate how PKA subunits are localized cells and tissues, and here we are using the retina as a “Window into the Brain”. Human mutations are also providing important clues that are allowing us to decipher how defects in PKA signaling can drive a variety of diseases. Our multi-scale approach that extends from solving high resolution structures to imaging in cells and tissues continues to lead to new discoveries that include non-canonical mechanisms for PKA signaling.

Registration for lunch with the speaker /for Ph.D. students/

The sponsored lunch usually takes place in the Campus River restaurant. Please meet the speaker and other students at 12:45 at the reception desk at the main entrance (building B22, see the map below).