Protein kinase A: a quirky prototype.

Protein kinase A (PKA) has served as a prototype for establishing kinase fundamentals, including sequence, structure and catalytic mechanism. However, PKA is quirky in some respects. Its regulatory elements are expressed separately, including type I (RI) regulatory subunits that contain unusual disulphide-linked dimerization and docking domains. Benjamin-Zukerman and colleagues report on the RIβ mutation L50R that disrupts this domain to cause neuronal loss and parkinsonism driven by a PKA mutation. They show that PKA catalytic subunits are released more easily from RIβ subunits containing the L50R mutation, adding depth to our understanding of this neurodevelopmental disorder.