High impact information on MKS1

• A hypophosphorylated form of Mks1p bound to Rtg2p is inactive [1].
• The inhibitory form of Mks1p is phosphorylated and complexed with the 14-3-3 proteins, Bmh1p and Bmh2p, which are also negative regulators of RS [1].
• Point mutations in the Rtg2p ATP binding domain simultaneously block RS and Mks1p-Rtg2p interaction [1].
• Analyses of transgenic plants and genome-wide transcript profiling indicated that MKS1 is required for full SA-dependent resistance in mpk4 mutants, and that overexpression of MKS1 in wild-type plants is sufficient to activate SA-dependent resistance, but does not interfere with induction of a defense gene by JA [2].
• Conversely, deletion of MKS1, which increases glutamate and glutamine synthesis, decreases Gap1p sorting to the plasma membrane [3].

Biological context of MKS1

• Two unresolved discrepancies exist with regard to the mechanism of RTG target gene control: (1) deletion of MKS1 results in constitutive expression of RTG target genes in most but not all strain backgrounds; and (2) RTG target gene expression has been correlated with both decreased as well as increased Rtg3p phosphorylation [4].
• Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes [5].
• Here we establish that the likely role of Rtg2 is to antagonize the activity of another protein, Mks1, which we demonstrate is itself a negative regulator of RTG target gene activation [6].
• The increased production of lysine in lys80 mutants appeared to result from an improvement of the metabolic flux through the pathway and was correlated to an increase of the alpha-ketoglutarate pool and of the level of several enzymes of the tricarboxylic acid cycle [7].

Anatomical context of MKS1

• In mks1 Delta cells, RTG target gene expression is constitutive, bypassing the requirement for Rtg2p, and is no longer repressible by glutamate [8].

Associations of MKS1 with chemical compounds

• This latter result provides a molecular explanation for the previous identification of MKS1 as LYS80, a negative regulator of lysine biosynthesis [8] [6].
• Moreover, overexpression of Ure2p suppresses the ability of Mks1p overexpression to allow ureidosuccinate uptake on ammonia [9].
• An mks1 ure2 double mutant can take up ureidosuccinate on either ammonia or proline [9].
• We find that glutamate suppresses [URE3] formation, suggesting that the Mks1p effect on the formation of [URE3] can occur indirectly via regulation of the RTG pathway [8].

Other interactions of MKS1

• We find that overproduction of Mks1p allows uptake of ureidosuccinate on ammonia and lack of Mks1p prevents uptake of ureidosuccinate or Dal5p expression on proline [9].
• First, we demonstrate that the mks1 deletion strain used in a previous study by Shamji and coworkers contains a nonsense mutation within codon Ser 231 in RTG3 that likely accounts for the inactivity of the RTG system in this strain [4].
• Overexpression of Mks1p does not affect cellular levels of Ure2p [9].
• Mks1p is negatively regulated by binding to Rtg2p and positively regulated when bound to Bmh1/2p [10].
• We show that Rtg2p controls RS by reversibly binding a negative regulator, Mks1p [1].

Analytical, diagnostic and therapeutic context of MKS1

• Gel filtration experiments indicate that both Rtg2p and Mks1p exist in high molecular weight complexes [11].

References