FUS3/YBL016W Summary Help

Standard Name FUS3
Systematic Name YBL016W
Alias DAC2 1
Feature Type ORF, Verified
Description Mitogen-activated serine/threonine protein kinase involved in mating; phosphoactivated by Ste7p; substrates include Ste12p, Far1p, Bni1p, Sst2p; inhibits invasive growth during mating by phosphorylating Tec1p, promoting its; inhibits recruitment of Ste5p, Cdc42p-mediated asymmetry and mating morphogenesis (2, 3, 4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description cell FUSion
Chromosomal Location
ChrII:192451 to 193512 | ORF Map | GBrowse
Gbrowse
Genetic position: -5 cM
Gene Ontology Annotations All FUS3 GO evidence and references
  View Computational GO annotations for FUS3
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
High-throughput
Regulators 9 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
overexpression
unspecified
Resources
445 total interaction(s) for 293 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 29
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 24
  • Biochemical Activity: 102
  • Co-crystal Structure: 2
  • Co-fractionation: 1
  • Co-localization: 2
  • FRET: 7
  • PCA: 2
  • Reconstituted Complex: 28
  • Two-hybrid: 20

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Rescue: 4
  • Negative Genetic: 91
  • Phenotypic Enhancement: 15
  • Phenotypic Suppression: 13
  • Positive Genetic: 82
  • Synthetic Growth Defect: 4
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 2
  • Synthetic Rescue: 9

Resources
Expression Summary
histogram
Resources
Length (a.a.) 353
Molecular Weight (Da) 40,772
Isoelectric Point (pI) 7.11
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:192451 to 193512 | ORF Map | GBrowse
SGD ORF map
Genetic position: -5 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1062 192451..193512 2011-02-03 1997-01-28
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 SGDIDS000000112
SUMMARY PARAGRAPH for FUS3

Fus3p is a member of the mitogen-activated protein kinase (MAPK) family of serine/threonine-specific kinases, which mediate phosphorylation reactions in signaling pathways that link receptor activation to control of cell proliferation (9). The S. cerevisiae genome encodes six MAP kinase-like proteins: Fus3p, Kss1p, Smk1p, Slt2p, Hog1p, and Ykl161p. Five of these are known to function in pathways that mediate mating, responses to nutrient deprivation, cell wall remodelling, and responses to osmolarity changes (reviewed in 10). MAPK pathways comprise a three-component module of kinases that is conserved from yeast to humans. These kinases activate in a sequential order, often referred to as a cascade: a MAPK kinase kinase (MEKK) activates a MAPK kinase (MEK), which activates a MAPK (reviewed in 10). In the mating pathway, Ste11p is the MEKK, Ste7p is the MEK, and both Fus3p and Kss1p are the MAPKs (reviewed in 11).

Haploid yeast cells, which exist as either MATa or MATalpha mating types, initiate mating to form diploids through production of peptide pheromones (a factor or alpha factor). Pheromones bind to seven-transmembrane receptor proteins on cells of the opposite type: Ste2p (MATa cells) or Ste3p (MATalpha cells) (12, 13), leading to activation of the heterotrimeric G-protein composed of alpha subunit Gpa1p, beta subunit Ste4p, and gamma subunit Ste18p (14, 15, 16). Activation is mediated by exchange of GDP for GTP on the alpha subunit, causing it to dissociate from the heterotrimer. The resulting Ste4p-Ste18p dimer recruits the scaffolding protein Ste5p and its associated MAP kinase cascade components, Ste11p, Ste7p, and Fus3p, to the membrane, where Ste11p is phosphorylated by the PAK kinase Ste20p (17, 18); Ste11p then phosphorylates Ste7p, which phosphorylates Fus3p and Kss1p (19, 20). Both MAPKs phosphorylate the transcription activator Ste12p, which induces a number of mating-specific genes; in addition, Fus3p phosphorylates the cell cycle regulator Far1p, which mediates cell cycle arrest and is also involved, with Cdc24p, in polarized growth toward the mating partner (2, reviewed in 11). This difference in substrate specificity between Fus3p and Kss1p is one factor that contributes to the greater importance of Fus3p in pheromone response, while Kss1p is more prominent in activating the filamentous growth pathway (see below; reviewed in 4). Two additional substrates of Fus3p include Bni1p, a formin homologue required for polarized growth (6), and Sst2p, which is involved in attenuating the signal (3).

The kinase cascade of Ste20p, Ste11p, and Ste7p, and the transcriptional activator Ste12p, function in mating and are also required for activating genes involved in filamentous growth; thus, the cell must have mechanisms for preventing inappropriate activation of either pathway (21). It has been shown that Fus3p inhibits filamentous growth during mating through degradation of Tec1p, which is a cofactor for Ste12p in the expresson of filamentation genes. During pheromone response, Fus3p phosphorylates a site in Tec1p, which leads to ubiquitination and degradation through an SCF ubiquitin protein ligase (22, 7). Tec1p is not a substrate for Kss1p, so Tec1p remains stable during filamentous growth (22). The scaffold protein Ste5p plays a role in insulating the mating pathway from the filamentation pathway, as shown by analysis of a point mutation in Ste5p that confers increased activation of Kss1p and reduced Fus3p-dependent degradation of Tec1p (23).

Phosphorylation of Fus3p in response to pheromone treatment is rapid and occurs at residues threonine-180 and tyrosine-182 (24). Pheromone also stimulates an increase in nuclear accumulation of Fus3p, which shuttles between the cytoplasm and nucleus in vegetative cells (25). Nuclear accumulation is reversed by interaction with Gpa1p and the phosphatase Msg5p; their action along with dephosphorylation of Fus3p by the phosphatase Ptp3p downregulates Fus3p and promotes recovery of cells from pheromone (26, 25).

Mitogen-activated protein kinases are widely conserved in eukaryotic cells. The closest human homolog to Fus3p is MAPK1 (also referred to as ERK2) with 51% identity (reviewed in 11).

Last updated: 2007-07-04 Contact SGD

References cited on this page View Complete Literature Guide for FUS3
1) Fujimura HA  (1992) The DAC2/FUS3 protein kinase is not essential for transcriptional activation of the mating pheromone response pathway in Saccharomyces cerevisiae. Mol Gen Genet 235(2-3):450-2
2) Elion EA, et al.  (1993) FUS3 phosphorylates multiple components of the mating signal transduction cascade: evidence for STE12 and FAR1. Mol Biol Cell 4(5):495-510
3) Garrison TR, et al.  (1999) Feedback phosphorylation of an RGS protein by MAP kinase in yeast. J Biol Chem 274(51):36387-91
4) Breitkreutz A and Tyers M  (2002) MAPK signaling specificity: it takes two to tango. Trends Cell Biol 12(6):254-7
5) Ptashne M and Gann A  (2003) Signal transduction. Imposing specificity on kinases. Science 299(5609):1025-7
6) Matheos D, et al.  (2004) Pheromone-induced polarization is dependent on the Fus3p MAPK acting through the formin Bni1p. J Cell Biol 165(1):99-109
7) Bao MZ, et al.  (2004) Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast. Cell 119(7):991-1000
8) Yu L, et al.  (2008) Counteractive Control of Polarized Morphogenesis during Mating by Mitogen-activated Protein Kinase Fus3 and G1 Cyclin-dependent Kinase. Mol Biol Cell 19(4):1739-52
9) Boulton TG, et al.  (1990) An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science 249(4964):64-7
10) Widmann C, et al.  (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79(1):143-80
11) Bardwell L  (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26(2):339-50
12) Burkholder AC and Hartwell LH  (1985) The yeast alpha-factor receptor: structural properties deduced from the sequence of the STE2 gene. Nucleic Acids Res 13(23):8463-75
13) Hagen DC, et al.  (1986) Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor: gene sequence and implications for the structure of the presumed receptor. Proc Natl Acad Sci U S A 83(5):1418-22
14) Whiteway M, et al.  (1989) The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein. Cell 56(3):467-77
15) Dietzel C and Kurjan J  (1987) The yeast SCG1 gene: a G alpha-like protein implicated in the a- and alpha-factor response pathway. Cell 50(7):1001-10
16) Miyajima I, et al.  (1987) GPA1, a haploid-specific essential gene, encodes a yeast homolog of mammalian G protein which may be involved in mating factor signal transduction. Cell 50(7):1011-9
17) 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
18) Dowell SJ, et al.  (1998) Mapping of a yeast G protein betagamma signaling interaction. Genetics 150(4):1407-17
19) 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
20) Ma D, et al.  (1995) Phosphorylation and localization of Kss1, a MAP kinase of the Saccharomyces cerevisiae pheromone response pathway. Mol Biol Cell 6(7):889-909
21) Roberts RL and Fink GR  (1994) Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth. Genes Dev 8(24):2974-85
22) Chou S, et al.  (2004) Fus3-regulated Tec1 degradation through SCFCdc4 determines MAPK signaling specificity during mating in yeast. Cell 119(7):981-90
23) Schwartz MA and Madhani HD  (2006) Control of MAPK signaling specificity by a conserved residue in the MEK-binding domain of the yeast scaffold protein Ste5. Curr Genet 49(6):351-63
24) Gartner A, et al.  (1992) Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1. Genes Dev 6(7):1280-92
25) Blackwell E, et al.  (2003) Effect of the pheromone-responsive G(alpha) and phosphatase proteins of Saccharomyces cerevisiae on the subcellular localization of the Fus3 mitogen-activated protein kinase. Mol Cell Biol 23(4):1135-50
26) Zhan XL, et al.  (1997) Differential regulation of FUS3 MAP kinase by tyrosine-specific phosphatases PTP2/PTP3 and dual-specificity phosphatase MSG5 in Saccharomyces cerevisiae. Genes Dev 11(13):1690-702