Disease relevance of CBK1

• We have studied the CBK1 gene of Saccharomyces cerevisiae, which encodes a conserved protein kinase similar to the human myotonic dystrophy kinase [1].

High impact information on CBK1

• We show that Cbk1 kinase and its interacting protein Mob2 regulate this asymmetry by inducing daughter-specific genetic programs [2].
• Daughter-specific expression is due to Cbk1/Mob2-dependent activation and localization of the Ace2 transcription factor to the daughter nucleus [2].
• Phosphoregulation of Cbk1 is critical for RAM network control of transcription and morphogenesis [3].
• In marked contrast, phosphorylation of a C-terminal hydrophobic motif is required for Cbk1 function in vivo but not for its kinase activity, suggesting a previously unappreciated level of control for this family of kinases [3].
• Previous work indicates that cells lacking the Dbf2p-related protein Cbk1p fail to sustain polarized growth during early bud morphogenesis and mating projection formation (Bidlingmaier, S., E.L. Weiss, C. Seidel, D.G. Drubin, and M. Snyder. 2001. Mol. Cell. Biol. 21:2449-2462) [4].

Biological context of CBK1

• We have found that mutations in MOB2 or CBK1 confer a slow-growth phenotype in a ras2Delta background [5].
• The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae [6].
• Epitope-tagged Cbk1p localizes to both sides of the bud neck in late anaphase, just prior to cell separation [6].
• Analysis of cbk1Delta cells reveals that Cbk1p is required for efficient apical growth, proper mating projection morphology, bipolar bud site selection in diploid cells, and cell separation [6].
• Site-directed mutations of serine-303 and threonine-494, potential regulatory phosphorylation sites in Pneumocystis CBK1, abolished mating projection formation, indicating a role for these amino acid residues in CBK1 activity [7].

Anatomical context of CBK1

• We further demonstrate that Pneumocystis CBK1 expressed in cbk1 Delta Saccharomyces cerevisiae cells restored defective cell wall separation during proliferation [7].
• Both Mob2p and Cbk1p localize interdependently to the bud cortex during polarized growth and to the bud neck and daughter cell nucleus during late mitosis [4].

Associations of CBK1 with chemical compounds

• The CBK1 gene, encoding a putative serine/threonine protein kinase, was identified in a screen designed to isolate mutations that affect apical growth [6].
• Conserved serine/threonine kinase encoded by CBK1 regulates expression of several hypha-associated transcripts and genes encoding cell wall proteins in Candida albicans [8].
• In addition, we show that increased trehalose accumulation and increased heat resistance caused by overexpression of LRE1 are also the result of inhibition of Cbk1, revealing a novel control pathway for certain targets affected by PKA [9].

Regulatory relationships of CBK1

• Consistent with this, Pneumocystis CBK1 expression also stimulated transcription of the CTS1 chitinase in cbk1 Delta mutant yeast cells, an event necessary for cell wall separation [7].
• The Saccharomyces cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell-specific localization of Ace2p transcription factor [4].

Other interactions of CBK1

• CBK1 and another gene, HYM1, were previously identified in a screen for genes involved in transcriptional repression and proposed to function in the same pathway [6].
• ACE2, CBK1, and BUD4 in budding and cell separation [10].
• Experiments examining budding patterns and sedimentation rates both show that Ace2 and Cbk1 have independent functions in addition to their common pathway in transcription of genes such as CTS1 [10].
• These genetic results suggest that PAG1 and CBK1 act in the same pathway [11].
• This is most evident for yeast genes CBK1, HRR25, and SNF1 and the kinase family S6K [12].

Analytical, diagnostic and therapeutic context of CBK1

• Herein, we report the identification of a cell wall biosynthesis kinase gene (CBK1) homologue in Pneumocystis carinii, isolated by differential display PCR, that is expressed optimally at physiological pH (7 to 8) as opposed to more acidic environments [7].

References