STE50/YCL032W Summary Help

Standard Name STE50 1
Systematic Name YCL032W
Feature Type ORF, Verified
Description Adaptor protein for various signaling pathways; involved in mating response, invasive/filamentous growth, osmotolerance; acts as an adaptor that links G protein-associated Cdc42p-Ste20p complex to the effector Ste11p to modulate signal transduction (2, 3 and see Summary Paragraph)
Name Description STErile 4
Chromosomal Location
ChrIII:63441 to 64481 | ORF Map | GBrowse
Gbrowse
Genetic position: -22 cM
Gene Ontology Annotations All STE50 GO evidence and references
  View Computational GO annotations for STE50
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Resources
Classical genetics
null
Large-scale survey
null
Resources
483 total interaction(s) for 384 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 13
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 8
  • Biochemical Activity: 5
  • Co-crystal Structure: 1
  • FRET: 1
  • PCA: 3
  • Protein-peptide: 1
  • Reconstituted Complex: 21
  • Two-hybrid: 92

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 3
  • Negative Genetic: 259
  • Phenotypic Enhancement: 9
  • Phenotypic Suppression: 4
  • Positive Genetic: 40
  • Synthetic Growth Defect: 9
  • Synthetic Lethality: 6
  • Synthetic Rescue: 6

Resources
Expression Summary
histogram
Resources
Length (a.a.) 346
Molecular Weight (Da) 38,970
Isoelectric Point (pI) 5.22
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIII:63441 to 64481 | ORF Map | GBrowse
SGD ORF map
Genetic position: -22 cM
Last Update Coordinates: 2000-09-13 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1041 63441..64481 2000-09-13 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000537
SUMMARY PARAGRAPH for STE50

The protein kinase regulator Ste50p is involved in mitogen-activated protein kinase (MAPK) pathways governing mating, filamentous growth, osmoregulation, and nitrogen starvation, all of which also depend on the MAPK kinase kinase (MAPKKK) Ste11p (5, 6, 7, 8, 9, 3). Ste50p and Ste11p interact constitutively via their N-terminal regions, each of which contains a single SAM domain, and Ste50p fulfills an essential role in the activation of the Sho1p branch of the high-osmolarity glycerol response (HOG) pathway by acting as an integral subunit of the Ste11p MAPKKK (5, 7, 10). The SAM domain, or Sterile Alpha Motif, is an evolutionarily-conserved protein-binding domain present in single copies in over 300 eukaryotic proteins (from fungi to mammals) that are involved in signal transduction, transcriptional activation and repression, and regulation of various developmental processes (11, 12). Effective regulation of Ste11p by Ste50p also depends on the Ste50p conserved C-terminal "Ras-association" (RA) domain, which is required for delivery of Ste11p to the plasma membrane in the filamentous growth signaling pathway, and is also essential for invasive growth and HOG signaling (13, 14). Ste50p disrupts an association between the Ste11p catalytic C-terminus and its regulatory N-terminus, and also appears to modulate Ste11p autophosphorylation and is itself a substrate of the Ste11p kinase (2). The interaction between Ste50p and Ste11p is a prerequisite for key signal transduction events, and is differentially required for Ste11p activity, as well as modulation of Ste11p function during mating, filamentous growth, and HOG signaling, but has a lesser role in pheromone response (5, 7, 13, 15).

Ste50p functions in cell signalling by determining the extent and duration of mating pheromone-induced signal transduction, thereby leading cells to hormone-induced differentiation, and acts downstream of the Ste2p alpha-pheromone receptor, between the pheromone receptor-bound heterotrimeric G protein (Galpha-beta-gamma) and Ste11p (3, 16). Ste50p serves as an adaptor that links the Cdc42p-Ste20p kinase complex to effector kinase Ste11p, by tethering Ste11p to the plasma membrane via association with Cdc42p, thereby permitting the encounter of Ste11p with Ste20p for activation, which is required for the intiation of signaling (3, 5, 13, 17).

Inactivation of STE50 leads to sterility and attenuation of mating pheromone-induced signal transduction, whereas overexpression of STE50 intensifies the pheromone-induced signaling (16, 4). Defects in filamentous growth and mating exhibited by ste50 mutants can be suppressed by the overexpression of STE11 (5). Mutations in the SAM domain of STE50 that prevent the heterotypic Ste11p-Ste50p association present signaling defects in the pathways for mating, filamentous growth and osmotolerance (7, 12, 9).

Homologs of STE50 are found in other fungi, including Saccharomyces kluyveri, Hansenula polymorpha, Candida albicans, and Neurospora crassa (3).

Last updated: 2006-06-22 Contact SGD

References cited on this page View Complete Literature Guide for STE50
1) Rad MR, et al.  (1991) The complete sequence of a 11,953 bp fragment from C1G on chromosome III encompasses four new open reading frames. Yeast 7(5):533-8
2) Wu C, et al.  (1999) Functional characterization of the interaction of Ste50p with Ste11p MAPKKK in Saccharomyces cerevisiae. Mol Biol Cell 10(7):2425-40
3) 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
4) Rad MR, et al.  (1992) STE50, a novel gene required for activation of conjugation at an early step in mating in Saccharomyces cerevisiae. Mol Gen Genet 236(1):145-54
5) Ramezani Rad M, et al.  (1998) Ste50p is involved in regulating filamentous growth in the yeast Saccharomyces cerevisiae and associates with Ste11p. Mol Gen Genet 259(1):29-38
6) 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
7) Jansen G, et al.  (2001) Mutations in the SAM domain of STE50 differentially influence the MAPK-mediated pathways for mating, filamentous growth and osmotolerance in Saccharomyces cerevisiae. Mol Genet Genomics 265(1):102-17
8) Wu C, et al.  (2003) Phosphorylation of the MAPKKK regulator Ste50p in Saccharomyces cerevisiae: a casein kinase I phosphorylation site is required for proper mating function. Eukaryot Cell 2(5):949-61
9) 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
10) Posas F, et al.  (1998) Requirement of STE50 for osmostress-induced activation of the STE11 mitogen-activated protein kinase kinase kinase in the high-osmolarity glycerol response pathway. Mol Cell Biol 18(10):5788-96
11) Ponting CP  (1995) SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins. Protein Sci 4(9):1928-30
12) 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
13) 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
14) 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
15) Kwan JJ, et al.  (2004) The solution structure of the S.cerevisiae Ste11 MAPKKK SAM domain and its partnership with Ste50. J Mol Biol 342(2):681-93
16) Xu G, et al.  (1996) Ste50p sustains mating pheromone-induced signal transduction in the yeast Saccharomyces cerevisiae. Mol Microbiol 20(4):773-83
17) Norman TC, et al.  (1999) Genetic selection of peptide inhibitors of biological pathways. Science 285(5427):591-5