High impact information on STE50

• Adaptor protein Ste50p links the Ste11p MEKK to the HOG pathway through plasma membrane association [1].
• We propose that Opy2p can serve as a membrane anchor for the Ste50p/Ste11p module in the activation of the HOG pathway [1].
• Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway [2].
• We found that strains with mutations in the STE50 gene, in combination with ssk2Delta ssk22Delta mutations, were unable to induce HOG1 phosphorylation after osmotic stress [3].
• Requirement of STE50 for osmostress-induced activation of the STE11 mitogen-activated protein kinase kinase kinase in the high-osmolarity glycerol response pathway [3].

Biological context of STE50

• STE50 has been shown to be involved in this pheromone signal-transduction pathway [4].
• A new gene, STE50, which plays an essential role in cell differentiation in Saccharomyces cerevisiae was detected and analysed [5].
• When present on a high copy number plasmid, STE50 causes supersensitivity to alpha-pheromone, and increases the level of alpha-pheromone-induced transcription of FUS1 in haploid a cells [5].
• These data indicate that inactivation of STE50 influences stress tolerance in mutants of the Ras-cAMP pathway, which is a major determinant of intrinsic stress tolerance and cell survival of the Saccharomyces cerevisiae [6].
• By pde2Delta-dependent increase of the Ras-cAMP pathway activity, inactivation of STE50 results in an extreme shortening of life span and oxidative stress sensitivity of sch9Delta mutants [6].

Anatomical context of STE50

• The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the plasma membrane in the filamentous growth signaling pathway of the yeast Saccharomyces cerevisiae [7].

Associations of STE50 with chemical compounds

• It was concluded that STE50 fulfills an essential role in the activation of the high-osmolarity glycerol response pathway by acting as an integral subunit of the STE11 MAPKKK [3].
• Replacement of T42 with a phosphorylation-mimetic aspartic acid residue (T42D) permits wild-type function in all assays of Ste50p function [8].
• Here, we show that Ste50p is phosphorylated on multiple serine/threonine residues in vivo [8].

Physical interactions of STE50

• Both two-hybrid analyses and coprecipitation assays demonstrated that the N-terminal domain of STE50 binds strongly to the N-terminal domain of STE11 [3].

Enzymatic interactions of STE50

• We show further that Hog1 phosphorylates Ste50 and that phosphorylation of Ste50 limits the duration of Kss1 activation and prevents invasive growth under high osmolarity growth conditions [9].

Regulatory relationships of STE50

• Overexpression of STE11 also suppresses the mating defects of ste50 mutants [10].
• RA domain function can be replaced by the nine C-terminal, plasma membrane-targeting residues (KKSKKCAIL) of Cdc42, and membrane-targeted Ste50 also suppresses the signaling deficiency of cdc42 alleles specifically defective in invasive growth [7].
• Moreover, when exposed to hyperosmolarity, these Ste50p-SAM mutants activate genes in the mating (FUS1) and filamentous-growth (FLO11) pathways to higher levels than does the wild type [11].
• This mutation abolishes the ability of overexpressed Ste50p to suppress either the mating defect of a ste20 ste50 deletion mutant or the mating defect of a strain with a Ste11p deleted from its sterile-alpha motif domain [8].

Other interactions of STE50

• We have found that L73A and L75A abrogate the Ste50p interaction with Ste11p, and we compare these data with the known interaction sites defined for other SAM domain interactions [12].
• Interestingly, these two Ste50p-SAM mutants were associated with increased activation of the mating and filamentous-growth pathways, but a reduction in the SHO1-dependent growth response to hyperosmolarity, relative to the wild-type Ste50p [11].
• Ste4 has regions of homology with STE50, an S. cerevisiae protein required for sexual differentiation that we show can bind to STE11 [13].
• In contrast, the constitutive activation of the pheromone response pathway caused by disruption of GPA1 (G alpha) is not suppressed in ste50-2 mutants [5].

Analytical, diagnostic and therapeutic context of STE50

• In a two-hybrid assay Ste50p interacts weakly with the G protein and strongly with the MAPKKK Ste11p [4].

References