Control of mitotic events by the Cdc42 GTPase, the Clb2 cyclin and a member of the PAK kinase family

Abstract

Previous studies have suggested that cyclin-dependent kinases control the cell cycle by directly phosphorylating proteins involved in specific events, such as nuclear lamins, microtubule-associated proteins and histones. In contrast, our results demonstrate that the Clb2-Cdc28 cyclin-dependent kinase complex controls specific cell-cycle events through a pathway that involves a GTPase and at least two different kinases. This suggests that cyclin-dependent kinases may control many cell-cycle events through GTPase-linked signaling pathways that resemble the intricate signaling pathways known to control many other cellular events.

Ybr267w is a New Cytoplasmic Protein Belonging to the Mitotic Signaling Network of Saccharomyces cerevisiae

“…These genes were reported to be required for Gin4 hyperphosphorylation or Gin4 kinase activity (Altman and Kellogg, 1997;Sreenivasan and Kellogg, 1999;Tjandra et al, 1998;Carroll et al, 1998). In Gin4 kinase assay using Histone H1 as substrate, a band of phosphorylated protein of the same as Gin4 was seen.…”

“…The following genes are known as genes encoding the negative regulators of Swe1 kinase: the septin genes (CDC3, CDC10, CDC11, CDC12 and SHS1), ELM1, NAP1, CLA4, HSL7 and the Nim1-related kinase genes (GIN4, HSL1 and KCC4) (Sreenivasan and Kellogg, 1999;Barral et al, 1999;Longtine et al, 2000;Shulewitz et al, 1999;Burton and Solomon, 2000). In a mutant of any of these genes, most probably due to the activation of Swe1 kinase, a bud retain its polar growth and consequently it becomes elongated (Altman and Kellogg, 1997;Tjandra et al, 1998). The pathway comprising these genes is called the mitotic signaling network.…”

“…In contrast to Nim1 of Schizosaccharomyces pombe, Nim1-related kinases of S. cerevisiae (Gin4, Hsl1 and Kcc4) are co-localized with septins at the bud neck (Tanaka and Nojima, 1996;Longtine et al, 1998;Barral et al, 1999;Okuzaki and Nojima, 2001) and have no major role in mitosis. Among Nim1-related kinases of S. cerevisiae, Gin4 has been the most extensively studied (Altman and Kellogg, 1997;Sreenivasan and Kellogg, 1999;Tjandra et al, 1998;Carroll et al, 1998;Longtine et al, 2000;Mortensen et al, 2002). Mortensen et al (2002) revealed a spatio-temporal sequence of Gin4 interaction with its regulators that leads to its dimerization and hyperphosphorylation.…”

Ras and the Rho Effector Cla4 Collaborate to Target and Anchor Lte1 at the Bud Cortex

“…5C, D). The lack of Lte1 phosphorylation was not due to a requirement of Ras for Cla4 activity since the phenotypes characteristic of cells lacking CLA4, such as a prolonged G 2 delay due to activation of the morphogenesis checkpoint 24,25 were not observed in ras1∆ras2∆ bcy1∆ triple mutants (Fig. 5B).…”

Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry

“…In Candida albicans, Gin4 is also phosphorylated and activated by Cdk1, and it has been shown that forced activation of Cdc42 restores defects in bud neck formation observed in gin4 mutants , placing Cdc42 downstream of the Gin4-Fpk1-flippase pathway, which is consistent with our findings. Interestingly, there is some evidence that Cdc42 itself is required in vivo for the mitosis-specific activation of Gin4 and the role it plays in polarized bud growth (Tjandra et al, 1998), which may represent an elegant feedback loop for regulation of the Gin4-Fpk1-flippase pathway.…”