Interview Seminar

Title：Assembly of Protein Kinase A Macromolecular Signaling Complexes

Speaker: Dr. Ping ZHANG, Ph.D.

Department of Pharmacology, University of California, San Diego

Time: 2:00pm, April 23rd

Venue: Rm. 411, New Life Sciences Building

Protein kinases are dynamically regulated signaling proteins that act as switches in the cell by phosphorylating target proteins. They are often tethered to large macromolecular complexes to provide tight spatiotemporal control. To understand the biological complexity of cell signaling, we need to understand how individual molecules function as part of large polyvalent and often highly dynamic signaling scaffolds at specific cellular locations. We apply an interdisciplinary approach that combines, x-ray crystallography, small angle scattering, electron microscopy, and kinetic methods to study a prototypical kinase, cyclic AMP-dependent protein kinase (PKA). PKA is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. The resting PKA holoenzyme is an R2:C2 heterotetramer, with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits. In mammalian cells there are four functionally non-redundant R-subunits (RI, RI, RII and RII), and these confer different structural features, subcellular localization, and biochemical properties.  I will present our recent work on the different quaternary structures of PKA holoenzymes, an isoform-specific myristylation switch that regulates PKA-membrane, and how autophosphorylation of RII creates a signaling cycle where phosphatases become an essential partner in PKA signaling complexes that provide precise reaction of the incoming stimuli.

Welcome!