Disease relevance of GSC2

• On the other hand, reverse substitution of the corresponding amino acid of Fks2p (I1355K) resulted in loss of hypersensitivity to aerothricin3 [corrected] [1].

High impact information on GSC2

• However, transcription of PMR2 and PMC1 was activated by only a subset of the treatments that activated FKS2 transcription [2].
• Moreover, the calcineurin-dependent transcriptional induction of FKS2 in response to Ca2+, alpha-factor, and Na+ was found to require CRZ1 [2].
• We describe new components of a calcineurin-mediated response in yeast, the Ca2+-induced transcriptional activation of FKS2, which encodes a beta-1,3 glucan synthase [2].
• A 24-bp region of the FKS2 promoter was defined as sufficient to confer calcineurin-dependent transcriptional induction on a minimal promoter in response to Ca2+ and was named CDRE (for calcineurin-dependent response element) [2].
• We find that 1,3-beta-glucan synthase activity is elevated in smk1 mutants, suggesting that SMK1 negatively regulates GSC2 [3].

Biological context of GSC2

• Fks1p and Fks2p are related proteins thought to be catalytic subunits of the beta-1,3-glucan synthase [4].
• The Smk1p MAP kinase negatively regulates Gsc2p, a 1,3-beta-glucan synthase, during spore wall morphogenesis in Saccharomyces cerevisiae [3].
• (vi) Treatment of S. cerevisiae with azole or terbinafine resulted in transcriptional upregulation of genes FKS2 and PMR1 known to be Ca2+ regulated [5].

Anatomical context of GSC2

• Moreover, FKS2 is also highly induced in response to pheromone in a calcineurin-dependent manner, suggesting that FKS2 may also play a role in the remodeling of the cell wall during the mating process [6].
• The Gtb1 protein was shown to be a soluble glycoprotein (96-102 kDa) localized to the endoplasmic reticulum lumen where it was present in a complex together with the yeast alpha-subunit homologue Gls2p [7].

Associations of GSC2 with chemical compounds

• We analysed Fks1p and Fks2p in beta-1,6-glucan deficient mutants and found that they were mislocalized and that the mutants had reduced in vitro glucan synthase activity, possibly contributing to the observed beta-1,6-glucan defects [4].
• In addition, eight out of 12 fks1ts fks2 delta mutants had altered beta-glucan levels at the permissive temperature: the partial killer resistant FKS1F1258Y N1520D allele was severely affected in both polymers and displayed a 55% reduction in beta-1,6-glucan, while the in vitro hyperactive allele FKS1T605I M761T increased both beta-glucan levels [4].
• Induction of FKS2 expression in response to pheromone, CaCl2, or loss of FKS1 function requires the Ca2+/calmodulin-dependent protein phosphatase calcineurin [8].
• These results suggest that the 1355th isoleucine of Fks2p plays a key role in aerothricin3 [corrected] sensitivity [1].
• Thus, although Gls2p is sufficient for cleavage of the penultimate glucose residue, Gtb1p is essential for cleavage of the final glucose [7].

Other interactions of GSC2

• Thus, the sensitivity of fks1 mutants to these drugs can be explained by the calcineurin-dependent transcription of FKS2 [6].
• Expression of FKS2 from the heterologous ADH1 promoter results in FK506-resistant growth [6].
• Yeast GS is composed of a putative catalytic subunit encoded by FKS1 and FKS2 and a regulatory subunit encoded by RHO1 [9].
• Integration of the glucan interaction network with the caspofungin data indicates an overlapping set of genes involved in FKS2 regulation, compensatory chitin synthesis, protein mannosylation, and the PKC1-dependent cell integrity pathway [10].
• With the exception of PHO89 and FKS2, none of the genes induced by Congo Red was up-regulated in a slt2 strain [11].

Analytical, diagnostic and therapeutic context of GSC2

• In order to identify essential amino acid residues responsible for the sensitivity, each of the 10 non-conserved amino acids of Fks1p was substituted into the corresponding amino acid of Fks2p by site-directed mutagenesis [1].

References