Aurora‐B and Rho‐kinase/ROCK, the two cleavage furrow kinases, independently regulate the progression of cytokinesis: possible existence of a novel cleavage furrow kinase phosphorylates ezrin/radixin/moesin (ERM)

Abstract

Cytokinesis is regulated by several protein kinases, such as Aurora-B and Rho-kinase/ROCK. We have indicated that these two kinases are the cleavage furrow (CF) kinases that accumulate at the cleavage furrow and phosphorylate several intermediate filament (IF) proteins into two daughter cells. It has been reported that Aurora-B phosphorylates MgcRacGAP to functionally convert to a RhoGAP during cytokinesis. Therefore, we investigated here the relationship between Aurora-B and Rho-kinase/ROCK in cytokinesis, by using small interfering RNA (siRNA) technique. Aurora-B depletion did not alter the cleavage furrow-specific localization of Rho-kinase/ROCK and vice versa. Treatment of Aurora-B or Rho-kinase/ROCK siRNA increased multinucleate cells, and the effect of double depletion was additive. Aurora-B depletion induced the reduction of cleavage furrow-specific phosphorylation of vimentin at Ser72 but not vimentin at Ser71, myosin light chain (MLC) at Ser19, and myosin binding subunit of myosin phosphatase (MBS) at Ser852. In contrast, Rho-kinase/ROCK depletion led to the reduction of cleavage furrow-specific phosphorylation of MLC at Ser19, MBS at Ser852, and vimentin at Ser71 but not vimentin at Ser72. Cleavage furrow-specific ezrin/radixin/moesin (ERM) phosphorylation was not altered in the Aurora-B-and/or Rho-kinase/ROCK-depleted cells. In addition, C3 or toxin B treatment did not abolish ERM phosphorylation at the cleavage furrow in cells attaining cytokinesis. These results suggest that Aurora-B and Rho-kinase/ROCK regulate the progression of cytokinesis without communicating to each other, and there may exist a novel protein kinase which phosphorylates ERM at the cleavage furrow.

Id1 Overexpression Induces Tetraploidization and Multiple Abnormal Mitotic Phenotypes by Modulating Aurora A

“…Stabilization of such proteins would also lead to significant mitotic perturbations such as defective microtubule-kinetochore interaction, disorganized interphase microtubules, supernumerary centrosomes, cytokinesis failure, and ploidy (Ota et al, 2002;Honda et al, 2003;Araki et al, 2004;Yokoyama et al, 2005). Some of these phenotypes were also observed in this study.…”

Myosin phosphatase target subunit: Many roles in cell function

“…They include (1) myosin II is a primary motor for cytokinesis [25,26]; (2) RLC phosphorylation rapidly increased in the midzone between the two separating sister chromatids just before the onset of, and throughout cytokinesis [27], and (3) MYPT1 phosphorylated at an inhibitory site is localized in cleavage furrows [24,28]. These observations suggest that MP is inhibited during cytokinesis, leading to an increase in RLC phosphorylation and myosin II activation.…”

“…Because MYPT1 appears to be phosphorylated at an inhibitory site at the cleavage furrows [24,28], and because RhoA is known to be critical for cytokinesis [37][38][39], the Rho/ ROK pathway is likely to be involved in the regulation of MP. Recent studies suggest an involvement of PLK1 in this signaling pathway [40,41].…”

Roles of Aurora Kinases in Mitosis and Tumorigenesis

“…Although the mechanism has not yet been elucidated, several substrates of Aurora-B were identified, including the type III intermediate filament desmin and vimentin (67,68), midbody component ZEN-4/MKLP1 (69,70), and other proteins like TACC1 (71) and MgcRacGAP (72). Aurora-B and Rho, a prominent regulator of cytokinesis, share certain substrates but exert phosphorylation independently, suggesting that Aurora-B and Rho might coordinate in cytokinesis control (73). Moreover, Aurora-B activates Rho by converting MgcRacGAP to a RhoGAP during cytokinesis (72), indicating that Aurora-B is multifunctional in cytokinesis regulation.…”