Figure 8. A model for Plk1-mediated generation of the midzone-derived signal for cell division.

In prometaphase, high Cdk1 levels maintain Ect2, centralspindlin, and PRC1 in a functionally inactive state. Upon Cdk1 inactivation at anaphase onset, the MKLP1 subunit of centralspindlin and PRC1 are dephosphorylated and thus able to bind and bundle antiparallel MT arrays to form the spindle midzone [12],[13]. At the same time, Plk1 is released from its early mitotic substrates by dephosphorylation of Cdk1-primed PBD docking sites, and inhibitory phosphorylation of Ect2 at Cdk1 sites is also reversed [14]. Plk1 then rapidly self-organizes onto the midzone via PBD- and activity-dependent positive-feedback loops involving multiple substrates, including PRC1 [36], MKLP2 [56], and HsCYK-4 (this study). Furthermore, in the case of HsCYK-4, Plk1 phosphorylation at S157 also creates a docking site for the tandem BRCT repeats of Ect2, thereby targeting the RhoGEF to the midzone and perhaps stimulating its activity [48]. The resulting increase in RhoA-GTP at the adjacent equatorial cortex promotes focal recruitment and activation of RhoA effectors needed for actin polymerization and myosin II motor activity within the contractile ring [2],[3].