SUMMARY PARAGRAPH for STE11
STE11 encodes a mitogen activated protein kinase kinase kinase (MAPKKK) which is involved in the MAPK pathways governing mating, osmosensing, and filamentous growth (reviewed in 6, 7, 8, 9). Although STE11 is not essential for viability, a null mutation in this gene results in sterility (10). STE11 homologs have been identified in yeasts such as Candida and Cryptococcus, and in Arabidopsis (11, 12, 13).
After exposure to pheromones, osmotic stress, or nutrient starvation, Ste11p is phosphorylated by the protein kinase Ste20p (14). Ste11p and Ste20p are brought together through the action of the adaptor protein Ste50p, which tethers Ste11p to the plasma membrane via association with the Rho-like GTPase Cdc42p (15, 16, 17 and references therein). During osmoregulation, plasma membrane association of Ste11p is further mediated by direct interactions with the osmotic signal receptor Sho1p (reviewed in 18 and 6).
Once activated, Ste11p phosphorylates the correct target MAPKK, either Ste7p for the mating and filamentous growth pathways or Pbs2p for the osmosensing pathway, via interactions with the scaffolding proteins Ste5p and Pbs2p, respectively. (19, 20). During pheromone response, Ste5p tethers Ste11p, Ste7p, and either of the MAPKs Fus3p or Kss1p. During osmoregulation, Pbs2p brings together Sho1p, Ste11p, the MAPK Hog1p, and also serves as the MAPKK target (21, and reviewed in 22).
Ste11p consists of a C-terminal kinase domain and three N-terminal regulatory domains: a sterile alpha motif (SAM) domain which binds to the Ste50p protein, a domain that interacts with Ste5p, followed by a catalytic-binding domain (CBD) that can bind and inhibit the activity of the C-terminus (reviewed in 7). Interaction of CBD with the catalytic domain is disrupted by the binding of Ste50p to the SAM domain and by Ste20p-mediated phosphorylation of serine and threonine residues in the CBD (23, 24). In response to pheromones, Ste11p is also regulated by ubiquitin-dependent protein degradation (25).
There are some discrepancies in STE11 literature as to the exact length of the protein since there are three in-frame ATGs in the STE11 coding sequence. Originally it was thought that translation begins at the first ATG, but it was later shown that the third ATG is the actual start codon (1).
Last updated: 2007-03-06