wis1 (SPBC409.07c, P33886) curation notes
Wis1 is the sole MAP kinase kinase (MAPKK/MAP2K, EC 2.7.12.2) of the fission-yeast
stress-activated (SAPK) Sty1/Spc1 pathway. It is a dual-specificity kinase that
phosphorylates and activates the MAPK Sty1/Spc1 on Thr-171 and Tyr-173 in response to
osmotic, oxidative, heat and nutrient stress. Wis1 is itself activated by phosphorylation
of its activation-loop residues Ser-469 and Thr-473 by the redundant MAPKKKs Wis4
(=Wik1/Wak1) and Win1; the pathway is scaffolded by the Mcs4 response regulator and the
Mak2/Mak3–Mpr1–Mcs4 phosphorelay (two-component system).
Key evidence
Identity / kinase domain / MAP kinase kinase activity
- Originally identified as a dosage-dependent mitotic regulator with ser/thr kinase homology
PMID:1756736
- It is a MAPKK (MEK) homolog most related to S. cerevisiae Pbs2
PMID:7859738
- Wis1 is the ONLY MAPKK that activates Spc1/Sty1 under stress
PMID:9718372
PMID:12181336
- Activates Spc1 via Thr-171/Tyr-173 (dual-specificity)
[PMID:12181336 "Wis1 activates Spc1 by phosphorylating threonine-171 and tyrosine-173" — phrased in 9585506 as: "Wis1 activates Spc1 by phosphorylating threonine-171 and tyrosine-173"]
- Activation requires phosphorylation of Wis1 Ser-469 and Thr-473 in its activation loop
PMID:12181336
PMID:9718372
Upstream MAPKKKs (Wis4, Win1)
Stress responses & downstream (Atf1)
- Spc1/Sty1 (downstream) activated by osmotic, oxidative, heat stress; Wis1 required
PMID:8649397
- Wis1-Spc1 pathway required for survival in heat, osmolarity, oxidation, nutrient limitation
PMID:9321395
- Osmostress and oxidative stress strongly activate Wis1; heat shock only weakly/transiently
PMID:10398679
- Atf1 transcription factor is the key nuclear substrate of the Sty1/Wis1 pathway
PMID:8824588
- Oxidative-stress signaling to the pathway via Mpr1-Mcs4 phosphorelay
PMID:10749922
Osmoregulation
- wis1 (=sty2) required for growth in high-osmolarity; deletion osmosensitive
PMID:7657164
- Conserved with HOG osmoregulatory pathway
PMID:7859738
- PP2C and Pyp phosphatases counteract the pathway (downstream / negative regulators)
Cell cycle / G2-M
- Dosage-dependent mitotic inducer; overexpression advances mitosis (small cell size)
PMID:1756736
- Links cell cycle G2/M to extracellular environment
PMID:7501024
Localization
- Wis1 is cytoplasmic (NES-dependent, Crm1 export); a fraction goes to nucleus on stress
PMID:9585506
PMID:12181336
PMID:12181336
- Cytoplasmic localization is required for Wis1 to enable nuclear targeting of Spc1.
Heterochromatin (non-core, indirect)
- MAPK pathway (via Atf1/Pcr1) contributes to Swi6/HP1 heterochromatin assembly at mat locus
PMID:15292231
This is an indirect, downstream consequence via Atf1; not a core molecular function of Wis1.
Curation conclusions
- Core MF: MAP kinase kinase activity (GO:0004708). Broad parents protein kinase activity /
protein serine/threonine kinase / protein serine kinase / protein tyrosine kinase /
ATP binding are correct but less informative.
- Core BP: stress-activated MAPK cascade / response to osmotic & oxidative stress.
GO:0038066 "p38MAPK cascade" is the term PomBase uses; acceptable but the Sty1 pathway is a
fungal SAPK analogous to p38 — keep but note it is the conventional term used.
- Core CC: cytosol/cytoplasm (IDA) and Mcs4 RR-MAPKKK complex (IDA/IPI).
- protein binding (GO:0005515 IPI) is uninformative -> mark over-annotated; the meaningful
interaction (Mcs4 complex) is already captured by GO:1990315.
- G2/M (GO:0010971) is real but dosage/genetic and is a non-core, indirect output of the SAPK
pathway. Keep as non-core.
- Heterochromatin (GO:0090055) is an indirect downstream pathway-level effect via Atf1/Pcr1 ->
keep as non-core.