Disease relevance of MID2

• Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression [1].

High impact information on MID2

• No genetic interactions were found between mid2 and the related gene mid1 [2].
• Here, we identified a protein Mid2p on the basis of its sequence similarity to S. pombe Mid1p, Saccharomyces cerevisiae Bud4p, and Candida albicans Int1p [2].
• Our data suggest that in yeast, O mannosylation increases the activity of Wsc1p, Wsc2p, and Mid2p by enhancing their stability [3].
• Aberrant processing of the WSC family and Mid2p cell surface sensors results in cell death of Saccharomyces cerevisiae O-mannosylation mutants [3].
• We demonstrate that Mid2 is not mannosylated in a pmt2 mutant and that this modification is important for signaling by Mid2 [4].

Biological context of MID2

• A role for MID2 in the cell integrity pathway is further supported by the finding that MID2 is required for induction of Mpk1p tyrosine phosphorylation during exposure to alpha-factor, calcofluor white, or high temperature [5].
• In addition, we have identified an open reading frame, MTL1, which encodes a protein with both structural and functional similarity to Mid2p [5].
• We conclude that Hcs77 is dedicated to signaling cell wall stress during vegetative growth and that Mid2 participates in this signaling, but its primary role is in signaling wall stress during pheromone-induced morphogenesis [6].
• Overexpression of MID2 suppresses the profilin-deficient phenotype of yeast cells [7].
• A high-copy-number plasmid containing MID2, which encodes a potential transmembrane protein involved in cell cycle control, suppresses the abnormal growth, actin distribution, alpha-factor maturation and the accumulation of intracellular membranous structures in pfy1delta cells [7].

Anatomical context of MID2

• The MID2 gene of Saccharomyces cerevisiae encodes a protein with structural features indicative of a plasma membrane-associated cell wall sensor [5].
• Another plasma membrane sensor, Mid2p, is known to rescue the rgd1Deltawsc1Delta synthetic lethality [8].

Associations of MID2 with chemical compounds

• The lack of the putative cell surface sensor Mid2 prevents vanadate- but not caffeine-induced Slt2 phosphorylation [9].
• Phosphorylation of Slt2p under such conditions is related to changes in the glycerol turnover and is mostly Mid2p dependent, suggesting that changes in cell turgor, mediated by intracellular accumulation of glycerol, are sensed by PKC sensors to promote the cell integrity response [10].

Physical interactions of MID2

• RGD1 genetically interacts with MID2 and SLG1, encoding two putative sensors for cell integrity signalling in Saccharomyces cerevisiae [11].

Regulatory relationships of MID2

• The Rgd1p Rho GTPase-activating protein and the Mid2p cell wall sensor are required at low pH for protein kinase C pathway activation and cell survival in Saccharomyces cerevisiae [12].

Other interactions of MID2

• It has been proposed that Wsc1p and Mid2p act upstream of the protein kinase C (PKC) pathway to function as mechanosensors of cell wall stress [8].
• The slight viability defect of rgd1 in minimal medium, which was exacerbated by mid2, was not osmoremediated [11].
• To further explore Mid2p signalling a two-hybrid screen was done using the cytoplasmic tail of Mid2p; this identified ZEO1 (YOL109w), encoding a 12 kDa peripheral membrane protein that localizes to the plasma membrane [13].
• Our data are consistent with a role for Mid2p in sensing cell wall stress and in activation of a response that includes both increased chitin synthesis and the Mpk1p mitogen-activated protein kinase cell integrity pathway [5].
• MID2 was isolated as a multicopy activator of the Skn7p transcription factor [5].

Analytical, diagnostic and therapeutic context of MID2

• Northern blot analysis showed that the expression of MID2 is stimulated threefold by mating pheromone [14].
• Downregulation of KAI1 has been found to be clinically associated with metastatic progression in a variety of cancers, whereas overexpression of CD82 specifically suppresses tumor metastasis in various animal models [1].

References