STE20
The STE20 group contains several pseudokinases, the best characterized being STRAD-alpha (STE20-related adaptor, STRADA). STRAD-alpha has lost catalytic residues yet adopts a closed, active-like conformation that binds and allosterically activates the tumor suppressor kinase LKB1 together with the scaffold MO25, licensing LKB1 to phosphorylate AMPK and control cellular energy balance. STRAD-alpha mutations cause PMSE syndrome, a disorder combining polyhydramnios, megalencephaly, and symptomatic epilepsy. Other STE20-related pseudokinases similarly act as adaptors within MAP4K networks rather than as enzymes. Recombinant STRAD-alpha and related proteins are used to reconstitute LKB1 complexes, probe pseudokinase-driven allostery, and study how a catalytically dead fold can license substrate phosphorylation by a partner kinase.
