  During M phase, Endosulfine (Endos) family proteins are phosphorylated by
Greatwall kinase (Gwl), and the resultant pEndos inhibits the phosphatase
PP2A-B55, which would otherwise prematurely reverse many CDK-driven
phosphorylations. We show here that PP2A-B55 is the enzyme responsible for
dephosphorylating pEndos during M phase exit. The kinetic parameters for
PP2A-B55's action on pEndos are orders of magnitude lower than those for
CDK-phosphorylated substrates, suggesting a simple model for PP2A-B55
regulation that we call inhibition by unfair competition. As the name suggests,
during M phase PP2A-B55's attention is diverted to pEndos, which binds much
more avidly and is dephosphorylated more slowly than other substrates. When Gwl
is inactivated during the M phase-to-interphase transition, the dynamic balance
changes: pEndos dephosphorylated by PP2A-B55 cannot be replaced, so the
phosphatase can refocus its attention on CDK-phosphorylated substrates. This
mechanism explains simultaneously how PP2A-B55 and Gwl together regulate
pEndos, and how pEndos controls PP2A-B55.
