STE20/YHL007C Summary Help

Standard Name STE20 1
Systematic Name YHL007C
Feature Type ORF, Verified
Description Cdc42p-activated signal transducing kinase; involved in pheromone response, pseudohyphal/invasive growth, vacuole inheritance, down-regulation of sterol uptake; GBB motif binds Ste4p; member of the PAK (p21-activated kinase) family (2, 3, 4, 5 and see Summary Paragraph)
Name Description STErile
Chromosomal Location
ChrVIII:97937 to 95118 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All STE20 GO evidence and references
  View Computational GO annotations for STE20
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
High-throughput
Regulators 8 genes
Resources
Classical genetics
null
overexpression
Large-scale survey
null
Resources
370 total interaction(s) for 233 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 12
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 25
  • Biochemical Activity: 98
  • Co-crystal Structure: 2
  • PCA: 14
  • Protein-peptide: 4
  • Reconstituted Complex: 8
  • Two-hybrid: 31

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 3
  • Dosage Rescue: 22
  • Negative Genetic: 27
  • Phenotypic Enhancement: 11
  • Phenotypic Suppression: 12
  • Positive Genetic: 26
  • Synthetic Growth Defect: 24
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 17
  • Synthetic Rescue: 27

Resources
Expression Summary
histogram
Resources
Length (a.a.) 939
Molecular Weight (Da) 102,361
Isoelectric Point (pI) 7.33
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:97937 to 95118 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2820 97937..95118 2011-02-03 1996-07-31
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 SGDIDS000000999
SUMMARY PARAGRAPH for STE20

STE20 encodes a serine threonine kinase that functions as a mitogen activated protein kinase (MAPK) kinase kinase kinase (MAPKKKK) and a histone serine kinase (6, 7). Originally identified in the yeast signaling pathway for mating (reviewed in 8), Ste20p has since been found to be involved in the MAPK pathways regulating osmosensing (9), filamentous growth (reviewed in 10), bud site selection (11), polarized growth (12, 13), actin organization (14, 15), regulation of exit from mitosis (16), and apoptosis (7). Although STE20 is not essential for viability, a null mutation in this gene results in sterility (17).

In its role in signal transduction, Ste20p is activated by the Rho-like GTPase Cdc42p. Cdc42p binds to the N-terminal CRIB (Cdc42p- Rac Interactive Binding) domain of Ste20p, localizing Ste20p to the plasma membrane at sites of polarized growth such as the bud and shmoo tip and relieving the autoinhibitory effect the CRIB domain has on the Ste20p C-terminal kinase domain (18, 19, 20 and references therein). Alleviation of inhibition results in Ste20p activation by autophosphorylation (18) or, during budding, phosphorylation by the cyclin dependent kinase-cyclin complexes Cdc28p-Cln1p and Cdc28p-Cln2p (21, 22). Activated Ste20p subsequently phosphorylates its target, the Ste11p MAPKKK (6, 23). Maximum Ste20p signaling activity is also dependent on its direct interactions with the scaffolding protein Bem1p and the heterotrimeric G protein beta subunit, Ste4p (24, 25). During filamentous growth, Ste20p activity is regulated by the protein methyltransferase Hsl7p (26).

More recently, Ste20p activity has been linked to chromatin condensation during apoptosis. Similar to what is seen in apoptotic mammalian cells, hydrogen peroxide-induced cell death in S. cerevisiae requires chromatin condensation resulting from H2B phosphorylation. Upon treatment with hydrogen peroxide, Ste20p translocates to the nucleus and directly phosphorylates serine 10 of histone 2B (encoded by HTB1 and HTB2), even though there is no apparent nuclear-localization signal present in the kinase (7 and references therein).

Ste20p is the founding member of a large group of protein kinases known as the p21-activated kinase (PAK) family, which is conserved from yeast to humans (reviewed in 27). The STE20 homolog in Candida glabrata and Ustilago maydis are required for pathogenicity (28, 29) and mutations in human homolog pak3 (OMIM) are associated with the disease X-linked mental retardation-30 (OMIM) (reviewed in 27).

Last updated: 2007-04-06 Contact SGD

References cited on this page View Complete Literature Guide for STE20
1) Leberer E, et al.  (1992) The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein beta gamma subunits to downstream signalling components. EMBO J 11(13):4815-24
2) Peter M, et al.  (1996) Functional analysis of the interaction between the small GTP binding protein Cdc42 and the Ste20 protein kinase in yeast. EMBO J 15(24):7046-59
3) Song J, et al.  (2001) Molecular interactions of the Gbeta binding domain of the Ste20p/PAK family of protein kinases. An isolated but fully functional Gbeta binding domain from Ste20p is only partially folded as shown by heteronuclear NMR spectroscopy. J Biol Chem 276(44):41205-12
4) Bartholomew CR and Hardy CF  (2009) p21-activated kinases Cla4 and Ste20 regulate vacuole inheritance in Saccharomyces cerevisiae. Eukaryot Cell 8(4):560-72
5) Lin M, et al.  (2009) The Cdc42 effectors Ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway. Mol Biol Cell 20(22):4826-37
6) 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
7) Ahn SH, et al.  (2005) Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell 120(1):25-36
8) Bardwell L  (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26(2):339-50
9) Raitt DC, et al.  (2000) Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J 19(17):4623-31
10) Gancedo JM  (2001) Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol Rev 25(1):107-23
11) Sheu YJ, et al.  (2000) Polarized growth controls cell shape and bipolar bud site selection in Saccharomyces cerevisiae. Mol Cell Biol 20(14):5235-47
12) Goehring AS, et al.  (2003) Synthetic lethal analysis implicates Ste20p, a p21-activated potein kinase, in polarisome activation. Mol Biol Cell 14(4):1501-16
13) Holly SP and Blumer KJ  (1999) PAK-family kinases regulate cell and actin polarization throughout the cell cycle of Saccharomyces cerevisiae. J Cell Biol 147(4):845-56
14) Wu C, et al.  (1997) The phosphorylation site for Ste20p-like protein kinases is essential for the function of myosin-I in yeast. J Biol Chem 272(49):30623-6
15) Eby JJ, et al.  (1998) Actin cytoskeleton organization regulated by the PAK family of protein kinases. Curr Biol 8(17):967-70
16) Hofken T and Schiebel E  (2002) A role for cell polarity proteins in mitotic exit. EMBO J 21(18):4851-62
17) Ramer SW and Davis RW  (1993) A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 90(2):452-6
18) Leberer E, et al.  (1997) Functional characterization of the Cdc42p binding domain of yeast Ste20p protein kinase. EMBO J 16(1):83-97
19) Ash J, et al.  (2003) Genetic analysis of the interface between Cdc42p and the CRIB domain of Ste20p in Saccharomyces cerevisiae. Genetics 163(1):9-20
20) Lamson RE, et al.  (2002) Cdc42 regulation of kinase activity and signaling by the yeast p21-activated kinase Ste20. Mol Cell Biol 22(9):2939-51
21) Oehlen LJ and Cross FR  (1998) Potential regulation of Ste20 function by the Cln1-Cdc28 and Cln2-Cdc28 cyclin-dependent protein kinases. J Biol Chem 273(39):25089-97
22) Wu C, et al.  (1998) Cell cycle- and Cln2p-Cdc28p-dependent phosphorylation of the yeast Ste20p protein kinase. J Biol Chem 273(43):28107-15
23) 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
24) Winters MJ and Pryciak PM  (2005) Interaction with the SH3 domain protein Bem1 regulates signaling by the Saccharomyces cerevisiae p21-activated kinase Ste20. Mol Cell Biol 25(6):2177-90
25) Leeuw T, et al.  (1998) Interaction of a G-protein beta-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature 391(6663):191-5
26) Fujita A, et al.  (1999) Hsl7p, a negative regulator of Ste20p protein kinase in the Saccharomyces cerevisiae filamentous growth-signaling pathway. Proc Natl Acad Sci U S A 96(15):8522-7
27) Hofmann C, et al.  (2004) The genetics of Pak. J Cell Sci 117(Pt 19):4343-54
28) Calcagno AM, et al.  (2004) Candida glabrata Ste20 is involved in maintaining cell wall integrity and adaptation to hypertonic stress, and is required for wild-type levels of virulence. Yeast 21(7):557-68
29) Smith DG, et al.  (2004) An ste20 homologue in Ustilago maydis plays a role in mating and pathogenicity. Eukaryot Cell 3(1):180-9