A collaborative work on PKA and AKAPs

While working in the John Scott lab I had the opportunity to participate in a story with Eileen Kennedy's group entitled PKA-Type I Selective Constrained Peptide Disruptors of AKAP Complexes.   Check it out!

A-Kinase Anchoring Proteins (AKAPs) coordinate complex signaling events by serving as spatiotemporal modulators of cAMP-dependent protein kinase activity in cells. Although AKAPs organize a plethora of diverse pathways, their cellular roles are often elusive due to the dynamic nature of these signaling complexes. AKAPs can interact with the type I or type II PKA holoenzymes by virtue of high-affinity interactions with the R-subunits. As a means to delineate AKAP-mediated PKA signaling in cells, we sought to develop isoform-selective disruptors of AKAP signaling. Here, we report the development of conformationally constrained peptides named RI-STapled Anchoring Disruptors (RI-STADs) that target the docking/dimerization domain of the type 1 regulatory subunit of PKA. These high-affinity peptides are isoform-selective for the RI isoforms, can outcompete binding by the classical AKAP disruptor Ht31, and can selectively displace RIα, but not RIIα, from binding the dual-specific AKAP149 complex. Importantly, these peptides are cell-permeable and disrupt Type I PKA-mediated phosphorylation events in the context of live cells. Hence, RI-STAD peptides are versatile cellular tools to selectively probe anchored type I PKA signaling events.

Human Nek7-interactor RGS2 is required for mitotic spindle organization.

Congrats to Edmarcia Elisa de Souza and all the affiliated authors at the University of Campinas, Brazil, on their accepted story entitled "Human Nek7-interactor RGS2 is required for mitotic spindle organization."  It was fun to have the chance to work with Edmarcia while we were in the Doxsey Lab on this.  Jorg Kobarg's group found that a cell cycle related kinase, Nek7, through its interaction with a regulator of G-protein signaling, RGS2, has an exciting new implication in spindle orientation and spindle pole maturation. Check it out! It's currently in press, but you can find a link to it through pub med or through Cell Cycle below:

Cell Cycle. 2015 Feb 9:0. [Epub ahead of print]
Human Nek7-interactor RGS2 is required for mitotic spindle organization.
Elisa de Souza E, Hehnly H, Perez AM, Vaz Meirelles G, Costa Smetana JH, Doxsey S, Kobarg J.

From Figure 6 of Edmarcia's paper where she illustrates nicely the loss of RGS2 causing a mitotic delay, failure, or asymmetric flattening of the two daughter cells (A).  We believe spindle misorientation that occurs during metaphase is contributing to the asymmetric flattening of the two daughter cells (B-C).