View from the PEAKs: Insights from structural studies on the PEAK family of pseudokinases.

The PEAK family of pseudokinase scaffolds, comprising PEAK1 (originally termed SgK269), PEAK2 (SgK223, the human orthologue of rat Pragmin) and PEAK3 (C19orf35), have emerged as important regulators and integrators of cellular signaling and also play oncogenic roles in a variety of human cancers. These proteins undergo both homo- and heterotypic association that act to diversify signal output. Recently, structural and functional characterization of PEAK3 and its protein-protein interactions have shed light on PEAK signaling dynamics and the interdependency of PEAK family members, how PEAK dimerization regulates the binding of downstream effectors, and how 14-3-3 binding acts to regulate PEAK3 signal output. These important advances form the basis of this review.