Cmk2, a novel serine/threonine kinase in fission yeast

Abstract

The cmk2 gene of Schizosaccharomyces pombe encodes a 504 amino acid protein kinase with sequence homology with the calmodulin-dependent protein kinase family. The cmk2 + gene is not essential for cell viability but overexpression of cmk2 + blocks the cell cycle at G2 phase and this inhibition is cdc2-dependent. The Cmk2 is a cytoplasmic protein expressed in a cell cycle-dependent manner, peaking at the G1/S boundary. Overexpression of Cmk2 suppresses ¢ssion yeast DNA replication checkpoint defects but not DNA damage checkpoint defects, suggesting that the G2 cell cycle arrest mediated by high levels of Cmk2 provides su⁄cient time to correct DNA replication alterations. ß

Oxidative stress response pathways: Fission yeast as archetype

“…These proteins have been linked to the post-transcriptional control of gene expression in mammals and yeast (Dahlkvist et al, 1994;Neininger et al, 2002). Fission yeast encodes two MAPKAPKs (Srk1/Mkp1 and Cmk2/Mkp2), which are calmodulin-dependent, dual specificity protein kinases (Alemany et al, 2002). Upon oxidative stress both MAPKAPKs are activated by phosphorylation in a Sty1-dependent manner (Figure 4), with the Srk1-Sty1 interaction being stronger than that of Cmk2-Sty1 (Asp & Sunnerhagen, 2003).…”

“…Moreover, it has been shown that the overexpression of a constitutively active form of the Cmk2 MAPKAPK results in low Cdc2 activity and eventually in G2 arrest (Alemany et al, 2002;Rasmussen & Rasmussen, 1994). In response to oxidative stress, Sty1 binds and phosphorylates Cmk2 at the single phosphorylation site (Thr-411) of the protein DOI: 10.3109/1040841X.2013.870968 (Sanchez-Piris et al, 2002.…”

“…In response to oxidative stress, Sty1 binds and phosphorylates Cmk2 at the single phosphorylation site (Thr-411) of the protein DOI: 10.3109/1040841X.2013.870968 (Sanchez-Piris et al, 2002. Cmk2 levels change during the cell cycle, with Cmk2 expression peaking at the end of mitosis and becoming negligible at the entry into the G2 phase (Alemany et al, 2002). Due to its Sty1-dependent regulation and its localization at the growth sites of the cell, Cmk2 has been suggested to play a role in cell morphogenesis when intracellular ROS levels are high (Alemany et al, 2002).…”

Fission Yeast Mitogen-Activated Protein Kinase Sty1 Interacts with Translation Factors

“…Hog1 is the sole stress-activated MAPK in budding yeast, and Sty1 is the sole stress-activated MAPK in fission yeast. In budding yeast, two paralogous genes encode the MAPKAPKs Rck1 and Rck2 (8), and in fission yeast the corresponding proteins are Mkp1/Srk1 and Mkp2/Cmk2 (1,3,36). Similar to the situation in mammalian cells, Hog1 forms a relatively stable complex with Rck2 in budding yeast (5) and Sty1 with Mkp1/Srk1 in fission yeast (3,36), and in both organisms, the MAPK phosphorylates the cognate downstream kinase when activated by stress (3-5, 36, 39).…”

Activation of Srk1 by the Mitogen-activated Protein Kinase Sty1/Spc1 Precedes Its Dissociation from the Kinase and Signals Its Degradation

“…In addition, Sty1/Spc1 binds and phosphorylates two downstream kinases, Cmk2 and Srk1 (Sty1-regulated kinase), which are related to the mammalian calmodulin-dependent kinases, MAPKAP kinases and to the budding yeast RCK1 and RCK2 kinases, which were identified as suppressors of a checkpoint mutant (Dahlkvist et al, 1995;Alemany et al, 2002;Smith et al, 2002).…”