KSS1/YGR040W Summary Help

Standard Name KSS1 1
Systematic Name YGR040W
Feature Type ORF, Verified
Description Mitogen-activated protein kinase (MAPK); involved in signal transduction pathways that control filamentous growth and pheromone response; the KSS1 gene is nonfunctional in S288C strains and functional in W303 strains (2, 3 and see Summary Paragraph)
Name Description Kinase Suppressor of Sst2 mutations 4
Chromosomal Location
ChrVII:575398 to 576504 | ORF Map | GBrowse
Gene Ontology Annotations All KSS1 GO evidence and references
  View Computational GO annotations for KSS1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Classical genetics
reduction of function
Large-scale survey
289 total interaction(s) for 176 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 49
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 19
  • Biochemical Activity: 69
  • FRET: 1
  • PCA: 8
  • Protein-peptide: 1
  • Reconstituted Complex: 30
  • Two-hybrid: 22

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Lethality: 1
  • Dosage Rescue: 3
  • Negative Genetic: 44
  • Phenotypic Enhancement: 12
  • Phenotypic Suppression: 18
  • Positive Genetic: 2
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 1
  • Synthetic Rescue: 3

Expression Summary
Length (a.a.) 368
Molecular Weight (Da) 42,692
Isoelectric Point (pI) 5.39
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVII:575398 to 576504 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1107 575398..576504 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003272

Kss1p 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 (5). The S. cerevisiae genome encodes six MAP kinase-like proteins: Fus3p, Kss1p, Smk1p, Slt2p, Hog1p, and Ykl161p, and 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 6). MAPK pathways comprise a three-component module of kinases that is conserved from yeast to humans. These kinases activate in a sequential order: a MAPK kinase kinase (MEKK) activates a MAPK kinase (MEK), which activates a MAPK (reviewed in 6). Kss1p participates in three signaling pathways that control haploid invasive (or diploid pseudohyphal) growth, pheromone response, and cell wall integrity (7, 8, 3, 9). In these pathways, Ste11p functions as the MEKK and Ste7p is the MEK (10, reviewed in 11 and 12).

The invasive growth pathway is activated when haploid cells are limited for carbon (diploid pseudohyphal growth is stimulated by nitrogen limitation) (10, reviewed in 13). This nutrient limitation activates Ras2p, which stimulates either of two pathways: a MAPK cascade or the cAMP-dependent protein kinase pathway (14). Kss1p functions in the MAPK pathway; it is phosphorylated and hence activated by Ste7p, leading to activation of the heteromeric transcription factor Tec1p-Ste12p and induction of target genes such as PGU1, MUC1, and CLN1 (15, 16). In its inactive unphosphorylated form, Kss1p binds to Ste12p and prevents it from activating genes involved in invasive growth (17, reviewed in 13). This same cascade functions to maintain cell wall integrity during vegetative growth (8, reviewed in 18).

Kss1p also plays a minor role, as part of the same MAPK pathway, in response to pheromones, which mediate mating of haploid yeast cells to form diploids (19). Mating is initiated by the binding of peptide pheromones (a factor or alpha factor) to seven-transmembrane receptor proteins on cells of the opposite type: Ste2p (MATa cells) or Ste3p (MATalpha cells) (20, 21). Receptor binding leads to activation of the heterotrimeric G-protein (alpha subunit Gpa1p, beta subunit Ste4p, gamma subunit Ste18p; 22, 23, 24). Activation leads to recruitment of the scaffolding protein Ste5p and its associated MAP kinase cascade components to the membrane, where Ste11p is phosphorylated by the PAK kinase Ste20p (25, 26); Ste11p then phosphorylates Ste7p, which phosphorylates Fus3p and Kss1p (27, 28). Both MAPKs phosphorylate the transcription activator Ste12p, which induces a number of mating-specific genes (reviewed in 11).

The difference in substrate specificity between Fus3p and Kss1p contributes to the greater importance of Fus3p in pheromone response, while Kss1p is more prominent in activating the invasive growth pathway (reviewed in 29). Fus3p also inhibits invasive growth during mating through degradation of Tec1p, which is a cofactor for Ste12p in the expression of filamentation genes. Tec1p is not a substrate for Kss1p, so Tec1p remains stable during filamentous growth (30). 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 (31).

Mitogen-activated protein kinases are widely conserved in eukaryotic cells. The closest human homolog to Kss1p is MAPK1 (also referred to as ERK2) with 50% identity (reviewed in 11).

Last updated: 2007-07-24 Contact SGD

References cited on this page View Complete Literature Guide for KSS1
1) Courchesne, W. and Thorner, J.  (1989) Personal Communication, Mortimer Map Edition 10
2) Madhani HD, et al.  (1997) MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation. Cell 91(5):673-84
3) Elion EA, et al.  (1991) FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction. Proc Natl Acad Sci U S A 88(21):9392-6
4) Courchesne WE, et al.  (1989) A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae. Cell 58(6):1107-19
5) Boulton TG, et al.  (1990) An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science 249(4964):64-7
6) 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
7) Cullen PJ, et al.  (2000) Defects in protein glycosylation cause SHO1-dependent activation of a STE12 signaling pathway in yeast. Genetics 155(3):1005-18
8) Lee BN and Elion EA  (1999) The MAPKKK Ste11 regulates vegetative growth through a kinase cascade of shared signaling components. Proc Natl Acad Sci U S A 96(22):12679-84
9) Cook JG, et al.  (1997) Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous-growth signalling pathway. Nature 390(6655):85-8
10) 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
11) Bardwell L  (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26(2):339-50
12) 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
13) Palecek SP, et al.  (2002) Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth. Microbiology 148(Pt 4):893-907
14) Mosch HU, et al.  (1999) Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae. Mol Biol Cell 10(5):1325-35
15) Madhani HD and Fink GR  (1997) Combinatorial control required for the specificity of yeast MAPK signaling. Science 275(5304):1314-7
16) Madhani HD, et al.  (1999) Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signaling mutants. Proc Natl Acad Sci U S A 96(22):12530-5
17) Bardwell L, et al.  (1998) Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK. Genes Dev 12(18):2887-98
18) Qi M and Elion EA  (2005) MAP kinase pathways. J Cell Sci 118(Pt 16):3569-72
19) Sabbagh W Jr, et al.  (2001) Specificity of MAP kinase signaling in yeast differentiation involves transient versus sustained MAPK activation. Mol Cell 8(3):683-91
20) 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
21) 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
22) 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
23) 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
24) 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
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) Dowell SJ, et al.  (1998) Mapping of a yeast G protein betagamma signaling interaction. Genetics 150(4):1407-17
27) 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
28) 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
29) Breitkreutz A and Tyers M  (2002) MAPK signaling specificity: it takes two to tango. Trends Cell Biol 12(6):254-7
30) Chou S, et al.  (2004) Fus3-regulated Tec1 degradation through SCFCdc4 determines MAPK signaling specificity during mating in yeast. Cell 119(7):981-90
31) 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