Disease relevance of RCK2

• Rck2 T379E was sufficiently inactive in an rck2Delta strain to allow some cells to survive PBS2DD toxicity even when overexpressed [1].

High impact information on RCK2

• In yeast, a CLK-1 homologue is absolutely required for ubiquinone biosynthesis and thus respiration [2].
• Here we show that CLK-1 is fully active when fused to green fluorescent protein and is found in the mitochondria of all somatic cells [2].
• Immunokinase assays showed that Hog1 can directly phosphorylate Rck2 to stimulate its enzymatic activity toward translation elongation factor 2 [3].
• Rck2, a member of the calmodulin-protein kinase family, links protein synthesis to high osmolarity MAP kinase signaling in budding yeast [3].
• Rck2 phosphorylation was transiently increased during osmostress or in mutants with a hyperactive high osmolarity glycerol (HOG) pathway [3].

Biological context of RCK2

• However, Clk1 shares 52% identity with Rck1, another putative protein kinase encoded in the S. cerevisiae genome [4].
• We find several proteins with a role in oxidative stress resistance using Rck1 or Rck2 as baits in a two-hybrid screen [5].
• We propose that one function of Rck1 and Rck2 is to inhibit meiosis [6].
• RCK1 has been mapped to the L arm of chromosome VII, and RCK2 to chromosome XII [7].
• The RCK1 and RCK2 protein kinase genes from Saccharomyces cerevisiae suppress cell cycle checkpoint mutations in Schizosaccharomyces pombe [8].

Anatomical context of RCK2

• Using immunofluorescence, Clk1 was localized to the cytosol and excluded from the nucleus [4].
• Rck2 is required for reprogramming of ribosomes during oxidative stress [9].

Associations of RCK2 with chemical compounds

• Some checkpoint mutants are sensitive to the DNA synthesis inhibitor hydroxyurea, and this sensitivity is also suppressed by RCK1 and RCK2 [8].
• We also studied the effect of replacing the predicted T379 and established S520 phosphorylation sites in Rck2p by glutamic acid [1].

Physical interactions of RCK2

• Both two-hybrid analyses and coprecipitation assays demonstrated that Hog1 binds strongly to the C-terminal region of Rck2 [10].

Regulatory relationships of RCK2

• This modification depended on catalytically active Hog1 kinase and two putative mitogen-activated protein kinase phosphorylation sites in Rck2 [3].

Other interactions of RCK2

• Consistently, growth arrest caused by hyperactivation of the Hog1 MAPK was abolished by deletion of the RCK2 gene [10].
• Degradation of Saccharomyces cervisiae Rck2 upon exposure of cells to high levels of zinc is dependent on Pep4 [11].

Analytical, diagnostic and therapeutic context of RCK2

• We have also identified a CLK2 autophosphorylation site, which is highly conserved among all CLK proteins, and we show by site-directed mutagenesis that its phosphorylation influences the subnuclear localization of CLK2 [12].
• Using active recombinant proteins and a surface plasmon resonance based detection technique, we demonstrated that the three members of this subfamily of kinases (CLK1, 2, and 4) all interact with beacon [13].

References