Disease relevance of GSY2

• We report that recombinant Pho85p and Pcl10p produced in Escherichia coli reconstitute an active Gsy2p kinase in vitro [1].

High impact information on GSY2

• It has been implicated in specifying the phosphorylation of glycogen synthase (Gsy2p) [1].
• The Arg residues in these two mutants are restricted to a highly conserved, 13-residue segment of Gsy2p that we propose to be important for glucose-6-P binding and/or the ability of the enzyme to undergo transitions between activity states [2].
• With wild type GSY2 placed under control of the ADH1 promoter, bcy1 cells did not accumulate glycogen despite increased GS-2 [3].
• Growth of cells in glycerol, however, resulted in constitutive expression of GSY2 mRNA and the corresponding protein, GS-2, suggestive of glucose repression of GSY2 [3].
• GSY1 resides on chromosome VI, and GSY2 is located on chromosome XII [4].

Biological context of GSY2

• In addition, the repressive effect of protein kinase A was quantitatively conserved when both STREs were mutated in GSY2 promoter, indicating that the negative control of gene expression by the RAS-cAMP signalling pathway does not act solely through STREs [5].
• We demonstrated that mutations of the HAP2/3/4 binding site and of the two STress-Responsive cis-Elements (STRE) did not abolish the early induction of GSY2, although the latter mutation led to a 20-fold drop in the transcriptional activity of the promoter, as determined from lacZ gene fusions [5].
• We show that the STress Responsive Elements (STREs) present in the promoter of GSY2 are essential for gene activation under conditions of stress, but dispensable for gene induction and glycogen accumulation at the diauxic shift on glucose [6].
• Analysis of Ser-to-Ala mutations at the three potential Gsy2p phosphorylation sites in pho85 cells implicated Ser-654 and/or Thr-667 in PHO85 control of glycogen synthase [7].
• Amino acid sequences obtained from a second polypeptide of 77 kDa present in yeast glycogen synthase preparations matched those predicted by GSY2 [4].

Associations of GSY2 with chemical compounds

• In cells grown on glucose, GSY2 mRNA levels increased approximately 10-fold during the transition from logarithmic to stationary phase [3].
• Alanine substitutions of three previously characterized phosphorylation sites in Gsy2p, Ser-650, Ser-654, or Thr-667, each suppressed the glycogen defect in cells unable to respire, suggesting that inactivation of this enzyme is mediated by phosphorylation of these residues [8].

Physical interactions of GSY2

• Yeast PIG genes: PIG1 encodes a putative type 1 phosphatase subunit that interacts with the yeast glycogen synthase Gsy2p [9].

Regulatory relationships of GSY2

• Two contiguous regions upstream of the GSY2 coding region are necessary for negative control by the cyclin-dependent protein kinase Pho85, one of which is a 14-bp G/C-rich sequence [6].

Other interactions of GSY2

• At least in the case of GSY2, regulation of transcription by Pho85 is not through the stress-responsive cis-promoter elements (STRE) [10].
• Cells carrying a disruption of the PHO85 gene inappropriately express both PHO5 and GSY2, resulting in the increase in phosphate scavenging and hyperaccumulation of glycogen in nutrient-rich conditions [10].
• Combinatorial control by the protein kinases PKA, PHO85 and SNF1 of transcriptional induction of the Saccharomyces cerevisiae GSY2 gene at the diauxic shift [6].
• The Msn2/4p branch, on the other hand, positively controls GSY2 expression directly through the STREs, and indirectly via a factor that still remains to be discovered [6].
• Enhanced viability under glucose deprivation conditions occurs when glycogen accumulates in the strain that overexpresses GSY2, which encodes glycogen synthase and maintains normal glycogen phosphorylase activity [11].

Analytical, diagnostic and therapeutic context of GSY2

• Northern blot analysis showed a parallel increase in the level of the GSY2 mRNA, which is consistent with transcriptional activation of GSY2 [12].
• Since no growth defect has been observed for strains with altered glycogen levels, the relative levels of fitness of GSY2 mutants that fail to accumulate glycogen and that hyperaccumulate glycogen were assayed by cocultivation experiments [13].

References