Biochemistry Seminar: Susan Taylor, "Lessons Learned and New Frontiers in PKA Signaling"

ZOOM LINK:

https://gc-cuny-edu.zoom.us/j/88065912335

Meeting ID: 880 6591 2335

ABSTRACT

In so many ways cAMP-dependent Protein Kinase (PKA) has pioneered the world of protein phosphorylation with the structure and function of the PKA catalytic (C) subunit serving as the prototype for the protein kinase superfamily. In addition to being captured at all stages of catalysis, the C-subunit has also captured the importance of dynamics in the entropy driven allosteric regulation of the kinase domain. To achieve this has required a highly interdisciplinary team approach. To then understand how the catalytic activity of PKA is regulated by cAMP, one needs to define how the kinase is trapped in an inhibited holoenzyme state by cAMP binding regulatory subunits. The full magnitude and allosteric complexity of activation has required both crystallography and cryo Electron Microscopy and is revealed most clearly by the recent cryoEM structure of the RIIb holoenzyme. However, to fully understand the complexity and specificity of PKA signaling in cells one needs to go beyond high resolution structures. Imaging of PKA in cells and tissues is also essential to appreciate the full magnitude and combinatorial diversity of PKA signalling. Here we discover at the bottom of the unexplored “dark” kinome the Cb isoform. While all of our understanding of PKA signaling to date comes from the Ca isoform, in tissues such as the brain at least 50% of PKA signaling is mediated by Cb, which includes many splice variants. The specificity and diversity of signaling by this forgotten isoform is revealing new frontiers in PKA signaling.