STE11/YLR362W Summary Help

Standard Name STE11
Systematic Name YLR362W
Feature Type ORF, Verified
Description Signal transducing MEK kinase; involved in pheromone response and pseudohyphal/invasive growth pathways where it phosphorylates Ste7p, and the high osmolarity response pathway, via phosphorylation of Pbs2p; regulated by Ste20p and Ste50p; protein abundance increases in response to DNA replication stress (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description STErile
Chromosomal Location
ChrXII:849866 to 852019 | ORF Map | GBrowse
Gbrowse
Genetic position: 244 cM
Gene Ontology Annotations All STE11 GO evidence and references
  View Computational GO annotations for STE11
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
Regulators 2 genes
Resources
Classical genetics
activation
conditional
null
Large-scale survey
null
Resources
242 total interaction(s) for 104 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 17
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 28
  • Biochemical Activity: 9
  • Co-crystal Structure: 3
  • Co-fractionation: 2
  • Co-purification: 1
  • FRET: 6
  • PCA: 8
  • Reconstituted Complex: 32
  • Two-hybrid: 33

Genetic Interactions
  • Dosage Rescue: 13
  • Phenotypic Enhancement: 18
  • Phenotypic Suppression: 48
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 6
  • Synthetic Rescue: 12

Resources
Expression Summary
histogram
Resources
Length (a.a.) 717
Molecular Weight (Da) 80,720
Isoelectric Point (pI) 7.19
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:849866 to 852019 | ORF Map | GBrowse
SGD ORF map
Genetic position: 244 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1999-07-17
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2154 849866..852019 2011-02-03 1999-07-17
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004354
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 Contact SGD

References cited on this page View Complete Literature Guide for STE11
1) Rhodes N, et al.  (1990) STE11 is a protein kinase required for cell-type-specific transcription and signal transduction in yeast. Genes Dev 4(11):1862-74
2) O'Rourke SM and Herskowitz I  (1998) The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev 12(18):2874-86
3) Neiman AM and Herskowitz I  (1994) Reconstitution of a yeast protein kinase cascade in vitro: activation of the yeast MEK homologue STE7 by STE11. Proc Natl Acad Sci U S A 91(8):3398-402
4) Grimshaw SJ, et al.  (2004) Structure of the sterile alpha motif (SAM) domain of the Saccharomyces cerevisiae mitogen-activated protein kinase pathway-modulating protein STE50 and analysis of its interaction with the STE11 SAM. J Biol Chem 279(3):2192-201
5) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
6) Westfall PJ, et al.  (2004) When the stress of your environment makes you go HOG wild. Science 306(5701):1511-2
7) Bardwell L  (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26(2):339-50
8) Wang Y and Dohlman HG  (2004) Pheromone signaling mechanisms in yeast: a prototypical sex machine. Science 306(5701):1508-9
9) Gancedo JM  (2001) Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol Rev 25(1):107-23
10) Shuster JR  (1982) Mating-defective ste mutations are suppressed by cell division cycle start mutations in Saccharomyces cerevisiae. Mol Cell Biol 2(9):1052-63
11) Calcagno AM, et al.  (2005) Candida glabrata Ste11 is involved in adaptation to hypertonic stress, maintenance of wild-type levels of filamentation and plays a role in virulence. Med Mycol 43(4):355-64
12) Clarke DL, et al.  (2001) The Cryptococcus neoformans STE11alpha gene is similar to other fungal mitogen-activated protein kinase kinase kinase (MAPKKK) genes but is mating type specific. Mol Microbiol 40(1):200-13
13) Covic L and Lew RR  (1996) Arabidopsis thaliana cDNA isolated by functional complementation shows homology to serine/threonine protein kinases. Biochim Biophys Acta 1305(3):125-9
14) Wu C, et al.  (1995) Molecular characterization of Ste20p, a potential mitogen-activated protein or extracellular signal-regulated kinase kinase (MEK) kinase kinase from Saccharomyces cerevisiae. J Biol Chem 270(27):15984-92
15) Wu C, et al.  (2006) Adaptor protein Ste50p links the Ste11p MEKK to the HOG pathway through plasma membrane association. Genes Dev 20(6):734-46
16) Truckses DM, et al.  (2006) 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. Mol Cell Biol 26(3):912-28
17) Kwan JJ, et al.  (2006) Saccharomyces cerevisiae Ste50 binds the MAPKKK Ste11 through a head-to-tail SAM domain interaction. J Mol Biol 356(1):142-54
18) Ramezani-Rad M  (2003) The role of adaptor protein Ste50-dependent regulation of the MAPKKK Ste11 in multiple signalling pathways of yeast. Curr Genet 43(3):161-70
19) Choi KY, et al.  (1994) Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae. Cell 78(3):499-512
20) Posas F and Saito H  (1997) Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science 276(5319):1702-5
21) Harris K, et al.  (2001) Role of scaffolds in MAP kinase pathway specificity revealed by custom design of pathway-dedicated signaling proteins. Curr Biol 11(23):1815-24
22) Ptashne M and Gann A  (2003) Signal transduction. Imposing specificity on kinases. Science 299(5609):1025-7
23) Bhattacharjya S, et al.  (2004) Solution structure of the dimeric SAM domain of MAPKKK Ste11 and its interactions with the adaptor protein Ste50 from the budding yeast: implications for Ste11 activation and signal transmission through the Ste50-Ste11 complex. J Mol Biol 344(4):1071-87
24) Drogen F, et al.  (2000) Phosphorylation of the MEKK Ste11p by the PAK-like kinase Ste20p is required for MAP kinase signaling in vivo. Curr Biol 10(11):630-9
25) Esch RK and Errede B  (2002) Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism. Proc Natl Acad Sci U S A 99(14):9160-5