Allosteric protein kinase regulation by pseudokinases: insights from STRAD

Abstract

Protein kinases regulate a plethora of diverse cellular functions. Their highly controlled activation is subject to an equally diverse repertoire of regulatory mechanisms. Pseudokinases, a class of proteins that possess a structurally related protein kinase domain that lacks phospho-transfer function, are emerging as critical yet mysterious regulators of other protein kinases. A new structural and functional analysis of the pseudokinase STRAD provides insight into the mechanism by which it allosterically regulates the catalytic function of the protein kinase LKB1 and hints at an evolution from a classical kinase-substrate relationship.