Ste11 (YLR362W) is the MEKK-family MAP kinase kinase kinase (MAP3K) of Saccharomyces cerevisiae, a Ser/Thr protein kinase with an N-terminal SAM domain and autoinhibitory region and a C-terminal kinase domain. It is shared by three MAPK pathways. In the pheromone response it phosphorylates and activates the MAPKK Ste7, which activates Fus3 (and Kss1), with the kinases assembled on the Ste5 scaffold. In the filamentous/invasive growth pathway it acts through Ste7 to activate Kss1. In the Sho1 branch of the high-osmolarity glycerol (HOG) pathway it phosphorylates the MAPKK Pbs2, which activates Hog1. Ste11 is activated when the PAK kinase Ste20 (or Cla4 in the HOG branch) phosphorylates its N-terminal regulatory region, relieving autoinhibition. It binds the adaptor Ste50 constitutively through a SAM-SAM interaction, and Ste50 links it to membrane-bound Cdc42 and Opy2. Pathway specificity comes from adaptors that pair Ste11 with its substrate: Ste5 with Ste7 for mating, and Sho1 with Pbs2 for osmosignaling. Ste11 is cytoplasmic and is transiently recruited to plasma-membrane signaling complexes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000196 cell integrity MAPK cascade | IGI PMID:10880465 Defects in protein glycosylation cause SHO1-dependent activa... | MARK AS OVER ANNOTATED | Summary: Cullen et al. (2000) found that glycosylation-defective mutants (e.g. dpm1) activate a Sho1-Ste20/Ste50-Ste11-Ste7-Kss1-Ste12 pathway, and that loss of pheromone-pathway components is synthetically sick with these mutants, suggesting this pathway contributes to cell wall integrity. Reason: GO:0000196 cell integrity MAPK cascade is defined as the MAPK cascade containing the Slt2 MAP kinase (Pkc1-Bck1-Mkk1/2-Slt2). The pathway implicated here is explicitly the Kss1 (filamentous growth) module, not the Slt2 cascade, so the genetic interaction with DPM1 supports a contribution of Ste11-dependent Kss1 signaling to cell wall maintenance rather than Ste11 acting as a tier of the Slt2 cascade. Reported Ste11-Mkk1 and Ste11-Slt2 links (Leng and Song 2016; Wang et al. 2011) are crosstalk. The biology is real but the term overstates Ste11's role; if kept it is non-core. Supporting Evidence: PMID:10880465 We specifically suggest that a Sho1 --> Ste20/Ste50 --> Ste11 --> Ste7 --> Kss1 --> Ste12 pathway is responsible for activation of FUS1 transcription in these mutants. PMID:10880465 we suggest that the Sho1 --> Ste12 pathway contributes to maintenance of cell wall integrity in vegetative cells file:yeast/STE11/STE11-deep-research-falcon.md Reported Cmk2 and Ptk2 connections are putative/context-dependent, and Mpk1/Slt2 activation is indirect |
| GO:0001402 signal transduction involved in filamentous growth | IMP PMID:8259520 Elements of the yeast pheromone response pathway required fo... | ACCEPT | Summary: Liu et al. (1993) showed that the pheromone-pathway kinases, including Ste11, and Ste12 are required for diploid filamentous (pseudohyphal) growth, independently of the pheromone receptor and G protein. Reason: Ste11 is the MAP3K of the Kss1 filamentous growth MAPK cascade (Ste20-Ste11-Ste7-Kss1), so it performs a signaling step in this pathway. This is one of Ste11's three core pathway roles. The newer term GO:0062031 filamentous growth MAPK cascade names Ste11 as its MAP3K in its definition and would be more precise (see suggested_questions), but GO:0001402 is the term SGD uses consistently for the other components (Ste7, Kss1, Ste20, Ste50), so it is accepted as is. Supporting Evidence: PMID:8259520 in diploids some of the same kinases and STE12 are required for filamentous growth PMID:8001818 the same components of the MAP kinase cascade necessary for diploid pseudohyphal development (STE20, STE11, STE7, and STE12) are also required for both filament formation and agar penetration in haploids |
| GO:0001403 invasive growth in response to glucose limitation | IMP PMID:8001818 Elements of a single MAP kinase cascade in Saccharomyces cer... | KEEP AS NON CORE | Summary: Roberts and Fink (1994) showed that STE20, STE11, STE7 and STE12 are required for haploid invasive growth (filament formation and agar penetration). Reason: Well-supported IMP. Invasive growth is a cellular/developmental outcome of the filamentous growth MAPK pathway in which Ste11 acts as the MAP3K; the signaling role is captured by GO:0001402, and the growth program itself is a downstream outcome, so kept as non-core. Supporting Evidence: PMID:8001818 the same components of the MAP kinase cascade necessary for diploid pseudohyphal development (STE20, STE11, STE7, and STE12) are also required for both filament formation and agar penetration in haploids |
| GO:0004672 protein kinase activity | HDA PMID:16319894 Global analysis of protein phosphorylation in yeast. | ACCEPT | Summary: Proteome-chip kinase assays (Ptacek et al. 2005) detected in vitro kinase activity of Ste11. Reason: Ste11 is a catalytically active protein kinase; the general term is correct. The more informative MAP kinase kinase kinase activity (GO:0004709) is annotated from focused IDA evidence. The chip substrates themselves are not necessarily physiological. Supporting Evidence: PMID:16319894 we identified over 4,000 phosphorylation events involving 1,325 different proteins PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAINT) inference of protein kinase activity for the MEKK-family node containing Ste11 and S. pombe Byr2. Reason: Correct, if general: Ste11 has a canonical Ser/Thr kinase domain and experimentally demonstrated kinase activity. Ste11 appearing among the WITH/FROM sources reflects its own experimental grounding. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt MAP kinase kinase kinase subfamily PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (Ser/Thr kinase active site) mapping to protein kinase activity. Reason: Correct general term, consistent with experimental MAP3K activity. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt MAP kinase kinase kinase subfamily PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:8159759 Reconstitution of a yeast protein kinase cascade in vitro: a... | ACCEPT | Summary: Neiman and Herskowitz (1994) reconstituted the Ste11-Ste7-Fus3 cascade in vitro with purified GST fusions: Ste11 phosphorylates and activates the MAPKK Ste7, and a Ste11-dependent phosphorylation site in Ste7 is required for Ste7 activity. Reason: Direct biochemical evidence for the defining molecular function of Ste11. Ste11 also phosphorylates the MAPKK Pbs2 in the Sho1 branch of HOG signaling. This is the core molecular function. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 PMID:8159759 We also identify a STE11-dependent phosphorylation site in STE7 which is required for activity of STE7. PMID:16778768 Ste11 phosphorylates residues in the activation loop of Pbs2, leading to its activation (step 8). |
| GO:0004709 MAP kinase kinase kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (ARBA, EC 2.7.11.25) of MAP kinase kinase kinase activity. Reason: Consistent with the experimentally established MAP3K activity of Ste11 on Ste7 and Pbs2. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt MAP kinase kinase kinase subfamily PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | MODIFY | Summary: Genome-wide yeast two-hybrid screen (Uetz et al. 2000) detected an interaction between Ste11 and its adaptor Ste50. Reason: Bare protein binding is uninformative. The Ste11-Ste50 interaction is well established in focused studies to be a constitutive heterotypic SAM-SAM domain interaction that is required for Ste11 function in the mating and Sho1-HOG pathways (Kwan et al. 2006; Wu et al. 1999). SAM domain binding (GO:0032093), already annotated to Ste11 by IDA, captures the functional content of this interaction. Proposed replacements: SAM domain binding Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. PMID:16337230 depends upon a direct interaction between the sterile alpha motif (SAM) domains of the Ste11 mitogen-activated protein kinase kinase kinase (MAPKKK) and its regulator Ste50 file:yeast/STE11/STE11-uniprot.txt Interacts (via SAM domain) with STE50 |
| GO:0005515 protein binding | IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro... | MODIFY | Summary: Comprehensive yeast two-hybrid analysis (Ito et al. 2001) detected an interaction between Ste11 and its adaptor Ste50. Reason: Bare protein binding is uninformative. The Ste11-Ste50 interaction is well established in focused studies to be a constitutive heterotypic SAM-SAM domain interaction that is required for Ste11 function in the mating and Sho1-HOG pathways (Kwan et al. 2006; Wu et al. 1999). SAM domain binding (GO:0032093), already annotated to Ste11 by IDA, captures the functional content of this interaction. Proposed replacements: SAM domain binding Supporting Evidence: PMID:11283351 Here we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins. PMID:16337230 depends upon a direct interaction between the sterile alpha motif (SAM) domains of the Ste11 mitogen-activated protein kinase kinase kinase (MAPKKK) and its regulator Ste50 file:yeast/STE11/STE11-uniprot.txt Interacts (via SAM domain) with STE50 |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: High-throughput MS complex identification (Ho et al. 2002) co-purified Ste11 with the MAPK Kss1. Reason: Bare protein binding is uninformative. The partner is one of the pheromone/filamentous growth MAP kinases (Fus3 or Kss1), which associate with Ste11 within the Ste5-organized multikinase complex. Mitogen-activated protein kinase binding (GO:0051019) states the partner class; the association is part of the MAPK module rather than a separate activity of Ste11, so it is non-core. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:11805837 Numerous protein complexes were identified, including many new interactions in various signalling pathways and in the DNA damage response. |
| GO:0005515 protein binding | IPI PMID:15020407 Fus1p interacts with components of the Hog1p mitogen-activat... | MODIFY | Summary: A two-hybrid matrix of fusion and pheromone-pathway proteins (Nelson et al. 2004) included a Ste11-Fus3 interaction. Reason: Bare protein binding is uninformative. The partner is one of the pheromone/filamentous growth MAP kinases (Fus3 or Kss1), which associate with Ste11 within the Ste5-organized multikinase complex. Mitogen-activated protein kinase binding (GO:0051019) states the partner class; the association is part of the MAPK module rather than a separate activity of Ste11, so it is non-core. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:15020407 A two-hybrid matrix containing fusion proteins and pheromone response pathway signaling molecules reveals that Fus1p may participate in a complex network of interactions. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MODIFY | Summary: Genome-wide TAP/MS complex purification (Gavin et al. 2006) detected an interaction between Ste11 and its adaptor Ste50. Reason: Bare protein binding is uninformative. The Ste11-Ste50 interaction is well established in focused studies to be a constitutive heterotypic SAM-SAM domain interaction that is required for Ste11 function in the mating and Sho1-HOG pathways (Kwan et al. 2006; Wu et al. 1999). SAM domain binding (GO:0032093), already annotated to Ste11 by IDA, captures the functional content of this interaction. Proposed replacements: SAM domain binding Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. PMID:16337230 depends upon a direct interaction between the sterile alpha motif (SAM) domains of the Ste11 mitogen-activated protein kinase kinase kinase (MAPKKK) and its regulator Ste50 file:yeast/STE11/STE11-uniprot.txt Interacts (via SAM domain) with STE50 |
| GO:0005515 protein binding | IPI PMID:16778768 Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osm... | MODIFY | Summary: Tatebayashi et al. (2006) showed that the Ste11-Ste50 complex binds the cytoplasmic domain of the osmosensor Sho1 (also directly, via Ste11 residues ~340-413, with activated Sho1 SH3 mutants), and that Sho1, which also binds Pbs2, acts as an adaptor bringing Ste11 together with its HOG-pathway substrate Pbs2. Reason: Bare protein binding is uninformative. The paper defines Sho1 as an adaptor/scaffold that simultaneously binds the Ste11-Ste50 complex and Pbs2 to channel Ste11 activity to Pbs2, analogous to Ste5 in mating. Scaffold protein binding (GO:0097110) captures this. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:16778768 the Ste11–Ste50 complex binds to the cytoplasmic domain of Sho1, to which Pbs2 also binds PMID:16778768 By the adaptor proteins (Sho1 and Ste5) that interact with both Ste11 and one of its substrate MAPKKs (Pbs2 and Ste7), Ste11 can thus change its MAPKK partners depending on the incoming stimulus. PMID:16778768 Thus, we can tentatively conclude that the catalytic domain-proximal region of Ste11N (residues 340–413) is important for the direct Ste11–Sho1 interaction |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Kinase-phosphatase interaction network AP-MS (Breitkreutz et al. 2010) detected an interaction between Ste11 and its adaptor Ste50. Reason: Bare protein binding is uninformative. The Ste11-Ste50 interaction is well established in focused studies to be a constitutive heterotypic SAM-SAM domain interaction that is required for Ste11 function in the mating and Sho1-HOG pathways (Kwan et al. 2006; Wu et al. 1999). SAM domain binding (GO:0032093), already annotated to Ste11 by IDA, captures the functional content of this interaction. Proposed replacements: SAM domain binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. PMID:16337230 depends upon a direct interaction between the sterile alpha motif (SAM) domains of the Ste11 mitogen-activated protein kinase kinase kinase (MAPKKK) and its regulator Ste50 file:yeast/STE11/STE11-uniprot.txt Interacts (via SAM domain) with STE50 |
| GO:0005515 protein binding | IPI PMID:26787465 Direct interaction of Ste11 and Mkk1/2 through Nst1 integrat... | MODIFY | Summary: Leng and Song (2016) reported an Nst1-mediated interaction between Ste11 and the CWI-pathway MAPKK Mkk1, proposed to link HOG/pheromone signaling to the Slt2 pathway under heat and pheromone. Reason: Bare protein binding is uninformative. The partner is a MAP kinase kinase, so mitogen-activated protein kinase kinase binding (GO:0031434) is the informative replacement. Only the abstract is available; the interaction represents crosstalk rather than a canonical Ste11 output and is non-core. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:26787465 Here, we identify a new interaction of Ste11 and Mkk1, mediated by Nst1 that connects the high-osmolarity glycerol and pheromone pathways directly to CWI pathway in response to heat and pheromone. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MODIFY | Summary: Proteome-wide affinity enrichment-MS interactome (Michaelis et al. 2023) detected an interaction between Ste11 and its adaptor Ste50. Reason: Bare protein binding is uninformative. The Ste11-Ste50 interaction is well established in focused studies to be a constitutive heterotypic SAM-SAM domain interaction that is required for Ste11 function in the mating and Sho1-HOG pathways (Kwan et al. 2006; Wu et al. 1999). SAM domain binding (GO:0032093), already annotated to Ste11 by IDA, captures the functional content of this interaction. Proposed replacements: SAM domain binding Supporting Evidence: PMID:37968396 AE–MS can define interactions between all complex members even if their interaction is not direct but bridged via other members PMID:16337230 depends upon a direct interaction between the sterile alpha motif (SAM) domains of the Ste11 mitogen-activated protein kinase kinase kinase (MAPKKK) and its regulator Ste50 file:yeast/STE11/STE11-uniprot.txt Interacts (via SAM domain) with STE50 |
| GO:0005515 protein binding | IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response... | MODIFY | Summary: Pairwise two-hybrid analysis of pheromone-pathway components (Printen and Sprague 1994) detected Ste11-Kss1 interaction. Reason: Bare protein binding is uninformative. The partner is one of the pheromone/filamentous growth MAP kinases (Fus3 or Kss1), which associate with Ste11 within the Ste5-organized multikinase complex. Mitogen-activated protein kinase binding (GO:0051019) states the partner class; the association is part of the MAPK module rather than a separate activity of Ste11, so it is non-core. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. |
| GO:0005515 protein binding | IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response... | MODIFY | Summary: Pairwise two-hybrid analysis of pheromone-pathway components (Printen and Sprague 1994) detected Ste11-Fus3 interaction. Reason: Bare protein binding is uninformative. The partner is one of the pheromone/filamentous growth MAP kinases (Fus3 or Kss1), which associate with Ste11 within the Ste5-organized multikinase complex. Mitogen-activated protein kinase binding (GO:0051019) states the partner class; the association is part of the MAPK module rather than a separate activity of Ste11, so it is non-core. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. |
| GO:0005515 protein binding | IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response... | MODIFY | Summary: Two-hybrid interaction of Ste11 with the pheromone-pathway scaffold Ste5 (Printen and Sprague 1994). Reason: Bare protein binding is uninformative. Ste5 is the pheromone-pathway scaffold that binds each kinase tier (Ste11, Ste7, Fus3) and is required for Ste11 function in mating; the Ste11 N-terminus binds Ste5. Scaffold protein binding (GO:0097110) captures the functional content: Ste11 is a client of the Ste5 scaffold, which routes its activity to Ste7. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:7851759 Ste5p, a protein of unknown biochemical function, interacted with protein kinases that operate at each step of the MAP kinase cascade, specifically with Ste11p (an MEKK), Ste7p (an MEK), and Fus3p (a MAP kinase). PMID:16778768 By the adaptor proteins (Sho1 and Ste5) that interact with both Ste11 and one of its substrate MAPKKs (Pbs2 and Ste7), Ste11 can thus change its MAPKK partners depending on the incoming stimulus. |
| GO:0005515 protein binding | IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc... | MODIFY | Summary: Choi et al. (1994) two-hybrid and co-purification analysis of the Ste5 multikinase complex; Ste11-Kss1 association. Reason: Bare protein binding is uninformative. The partner is one of the pheromone/filamentous growth MAP kinases (Fus3 or Kss1), which associate with Ste11 within the Ste5-organized multikinase complex. Mitogen-activated protein kinase binding (GO:0051019) states the partner class; the association is part of the MAPK module rather than a separate activity of Ste11, so it is non-core. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:8062390 By two-hybrid analysis, Ste11, Ste7, and Fus3 associate with different domains of Ste5, while Kss1, another MAPK, associates with the same domain as Fus3 |
| GO:0005515 protein binding | IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc... | MODIFY | Summary: Choi et al. (1994) showed Ste11 in a complex with Fus3, promoted by the Ste5 scaffold. Reason: Bare protein binding is uninformative. The partner is one of the pheromone/filamentous growth MAP kinases (Fus3 or Kss1), which associate with Ste11 within the Ste5-organized multikinase complex. Mitogen-activated protein kinase binding (GO:0051019) states the partner class; the association is part of the MAPK module rather than a separate activity of Ste11, so it is non-core. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:8062390 Ste5 also increases the amount of Ste11 complexed to Ste7 and Fus3 and is required for Ste11 to function. |
| GO:0005515 protein binding | IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc... | MODIFY | Summary: Ste11 binds and co-purifies with the Ste5 scaffold, which is required for Ste11 function in mating (Choi et al. 1994). Reason: Bare protein binding is uninformative. Ste5 is the pheromone-pathway scaffold that binds each kinase tier (Ste11, Ste7, Fus3) and is required for Ste11 function in mating; the Ste11 N-terminus binds Ste5. Scaffold protein binding (GO:0097110) captures the functional content: Ste11 is a client of the Ste5 scaffold, which routes its activity to Ste7. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:8062390 Ste5 copurifies with Ste11, Fus3, and a hypophosphorylated form of Ste7 PMID:8062390 Ste5 also increases the amount of Ste11 complexed to Ste7 and Fus3 and is required for Ste11 to function. PMID:16778768 By the adaptor proteins (Sho1 and Ste5) that interact with both Ste11 and one of its substrate MAPKKs (Pbs2 and Ste7), Ste11 can thus change its MAPKK partners depending on the incoming stimulus. |
| GO:0005515 protein binding | IPI PMID:9311911 Ste5 RING-H2 domain: role in Ste4-promoted oligomerization f... | MODIFY | Summary: In vitro binding of Ste5 (including a RING-H2 mutant) to each MAPK cascade component, including Ste11 (Inouye et al. 1997). Reason: Bare protein binding is uninformative. Ste5 is the pheromone-pathway scaffold that binds each kinase tier (Ste11, Ste7, Fus3) and is required for Ste11 function in mating; the Ste11 N-terminus binds Ste5. Scaffold protein binding (GO:0097110) captures the functional content: Ste11 is a client of the Ste5 scaffold, which routes its activity to Ste7. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:9311911 Ste5 is a scaffold for the mitogen-activated protein kinase (MAPK) cascade components in a yeast pheromone response pathway. PMID:9311911 In vitro Ste5(C177A C180A) bound each component of the MAPK cascade, but not Ste4. PMID:16778768 By the adaptor proteins (Sho1 and Ste5) that interact with both Ste11 and one of its substrate MAPKKs (Pbs2 and Ste7), Ste11 can thus change its MAPKK partners depending on the incoming stimulus. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based ATP binding (protein kinase ATP-binding site). Reason: Ste11 has a canonical kinase ATP-binding site and is an ATP-dependent kinase; correct. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt /ligand="ATP" file:yeast/STE11/STE11-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:0005737 cytoplasm | IDA PMID:9755161 Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires ... | ACCEPT | Summary: GFP-Ste11 localizes to the cytoplasm of unstressed cells and, unlike Hog1, does not enter the nucleus upon osmotic stress (Ferrigno et al. 1998). Reason: Direct localization evidence; Ste11 acts as a cytoplasmic kinase that is transiently recruited to cortical signaling complexes (via Ste5, Ste50/Cdc42 and Sho1). Supporting Evidence: PMID:9755161 we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells PMID:9755161 Following osmotic stress, HOG1, but neither PBS2 nor STE11, translocates into the nucleus. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-based cytoplasm localization. Reason: Consistent with experimental GFP localization. Supporting Evidence: PMID:9755161 we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells |
| GO:0007124 pseudohyphal growth | IMP PMID:8259520 Elements of the yeast pheromone response pathway required fo... | KEEP AS NON CORE | Summary: Ste11 is required for diploid pseudohyphal (filamentous) growth (Liu et al. 1993). Reason: Pseudohyphal growth is the developmental outcome of Kss1 filamentous-growth MAPK signaling, in which Ste11 acts as MAP3K. The requirement is well supported, but Ste11's contribution is the signaling step (GO:0001402), so this outcome process is non-core. Supporting Evidence: PMID:8259520 in diploids some of the same kinases and STE12 are required for filamentous growth |
| GO:0007232 osmosensory signaling pathway via Sho1 osmosensor | IGI PMID:9180081 Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK... | ACCEPT | Summary: Posas and Saito (1997) showed that the Sho1 osmosensor activates Pbs2 and Hog1 through the Ste11 MAPKKK; Ste11 is required for Sho1-branch signaling in cells lacking the redundant Ssk2/Ssk22 MAPKKKs. Reason: Ste11 is the MAP3K of the Sho1 branch of the HOG pathway, phosphorylating Pbs2. The IGI with SSK2/SSK22 reflects branch redundancy. Core pathway role. Supporting Evidence: PMID:9180081 A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. PMID:16778768 Ste11 phosphorylates residues in the activation loop of Pbs2, leading to its activation (step 8). |
| GO:0032093 SAM domain binding | IDA PMID:16337230 Saccharomyces cerevisiae Ste50 binds the MAPKKK Ste11 throug... | ACCEPT | Summary: NMR and mutational analysis show a head-to-tail heterotypic interaction between the Ste11 SAM domain and the Ste50 SAM domain (Kwan et al. 2006). Reason: Direct evidence; SAM-SAM binding to the adaptor Ste50 is required for Ste11 signaling in mating and high-osmolarity growth. This binding supports (rather than constitutes) the core catalytic MAP3K function, but is an accurate and informative MF. Supporting Evidence: PMID:16337230 depends upon a direct interaction between the sterile alpha motif (SAM) domains of the Ste11 mitogen-activated protein kinase kinase kinase (MAPKKK) and its regulator Ste50 PMID:16337230 Yeast bearing mutations that prevented the heterotypic Ste11-Ste50 association in vitro presented signaling defects in the mating and high-osmolarity growth pathways. |
| GO:0038066 p38MAPK cascade | IGI PMID:9180081 Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK... | ACCEPT | Summary: Ste11 activates the Pbs2-Hog1 (p38-type) MAPK cascade in the Sho1 branch; genetic interaction with ssk2 ssk22 (Posas and Saito 1997). Reason: GO:0038066 p38MAPK cascade explicitly includes the Hog1 cascade in yeast and starts with activation of a MAP3K. Ste11 is one of the three MAP3Ks of this cascade (with Ssk2/Ssk22) and phosphorylates Pbs2. Core. Supporting Evidence: PMID:9180081 A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. PMID:16778768 Ste11 phosphorylates residues in the activation loop of Pbs2, leading to its activation (step 8). |
| GO:0038066 p38MAPK cascade | IMP PMID:9180081 Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK... | ACCEPT | Summary: Mutant analysis places Ste11 as the MAP3K upstream of Pbs2 and Hog1 in the Sho1 branch (Posas and Saito 1997). Reason: Same evidence as the IGI row; Ste11 is a MAP3K tier of the Hog1 cascade. Core. Supporting Evidence: PMID:9180081 A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. |
| GO:0042802 identical protein binding | IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response... | KEEP AS NON CORE | Summary: IntAct-curated Ste11 self-interaction from the pairwise two-hybrid study of pheromone-pathway components (Printen and Sprague 1994). Reason: UniProt considers Ste11 a probable homodimer, and its SAM domain can make homotypic contacts (Kwan et al. 2006 note competing homotypic interactions). The abstract does not describe the self-interaction, but the curator read the full text. Self-association is not known to be central to Ste11 function; kept as non-core. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt Homodimer (Probable) PMID:7851759 Pathway components Ste4p, Ste5p, Ste7p, Ste11p, Ste12p, Ste20p, Fus3p and Kss1p were tested in all pairwise combinations. |
| GO:0042802 identical protein binding | IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc... | KEEP AS NON CORE | Summary: IntAct-curated Ste11 self-interaction from two-hybrid/co-purification analysis of the Ste5 complex (Choi et al. 1994). Reason: Consistent with the probable homodimer noted by UniProt; full text not available here, but the curated interaction is plausible. Not a core function. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt Homodimer (Probable) PMID:8062390 Ste5 forms a multikinase complex that joins these kinases for efficient Fus3 activation |
| GO:0042802 identical protein binding | IPI PMID:8670882 Identification of a novel Rac1-interacting protein involved ... | UNDECIDED | Summary: IntAct-curated Ste11 self-interaction citing Van Aelst et al. (1996), a paper describing the mammalian Rac1-interacting protein POR1. Reason: The cached abstract concerns mammalian Rac1/POR1 and does not mention Ste11; the Ste11 self-interaction may come from a yeast two-hybrid control or supplementary experiment in the full text, which is not available here. Following the rule not to overrule curators from incomplete evidence, this is left UNDECIDED rather than removed. The self-interaction itself is plausible (probable homodimer). Supporting Evidence: PMID:8670882 POR1 binds directly to Rac1 file:yeast/STE11/STE11-uniprot.txt Homodimer (Probable) |
| GO:0071474 cellular hyperosmotic response | IGI PMID:9180081 Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK... | KEEP AS NON CORE | Summary: ssk2 ssk22 ste11 cells are osmosensitive, showing that Ste11 (via the Sho1 branch) contributes to the cellular response to hyperosmotic stress (Posas and Saito 1997). Reason: Correct but broad: Ste11's contribution to the hyperosmotic response is its MAP3K step in the Sho1 branch, captured more precisely by GO:0007232 and GO:0038066. Kept as non-core. Supporting Evidence: PMID:9180081 A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. |
| GO:0071474 cellular hyperosmotic response | IMP PMID:9180081 Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK... | KEEP AS NON CORE | Summary: Ste11 mutant analysis in the Sho1 branch of the HOG pathway (Posas and Saito 1997). Reason: As for the IGI row; the more specific signaling terms carry the core role. Supporting Evidence: PMID:9180081 A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. |
| GO:0071507 pheromone response MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of pheromone response MAPK cascade from the Ste11/Byr2 clade (S. pombe Byr2 is the MAP3K of the fission yeast pheromone pathway). Reason: Consistent with extensive experimental evidence; Ste11 is the MAP3K of this cascade. Core. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 PMID:8455599 This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. |
| GO:0071507 pheromone response MAPK cascade | IDA PMID:8159759 Reconstitution of a yeast protein kinase cascade in vitro: a... | ACCEPT | Summary: In vitro reconstitution of the Ste11-Ste7-Fus3 pheromone-response kinase cascade (Neiman and Herskowitz 1994). Reason: Ste11 performs the MAP3K step of the pheromone response MAPK cascade; the GO definition names Ste11 as the MAP3K. Core. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0071507 pheromone response MAPK cascade | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-based annotation to pheromone response MAPK cascade. Reason: Consistent with experimental evidence. Core. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0071507 pheromone response MAPK cascade | IGI PMID:8455599 Pheromone-induced signal transduction in Saccharomyces cerev... | ACCEPT | Summary: Zhou et al. (1993) genetically ordered Ste11 upstream of Ste7 (IGI with STE7) in pheromone signaling. Reason: Genetic ordering evidence for Ste11 as MAP3K of the pheromone cascade. Core. Supporting Evidence: PMID:8455599 This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. |
| GO:0071507 pheromone response MAPK cascade | IMP PMID:8159759 Reconstitution of a yeast protein kinase cascade in vitro: a... | ACCEPT | Summary: Mutational analysis (Neiman and Herskowitz 1994) including a Ste11-dependent activating site in Ste7. Reason: Supports Ste11 as the MAP3K of the pheromone cascade. Core. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
| GO:0071507 pheromone response MAPK cascade | IMP PMID:8455599 Pheromone-induced signal transduction in Saccharomyces cerev... | ACCEPT | Summary: ste11 mutants fail to hyperphosphorylate/activate Ste7 during pheromone induction (Zhou et al. 1993). Reason: Supports Ste11 as the MAP3K of the pheromone cascade. Core. Supporting Evidence: PMID:8455599 This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. PMID:8455599 Among the components necessary for signal transduction are the STE7 and STE11 kinases and either one of the redundant FUS3 and KSS1 kinases. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based protein serine kinase activity (RHEA:17989). Reason: Ste11 is a Ser/Thr MAP3K; its activating phosphorylation of MAPKKs targets Ser/Thr residues in the activation loop. Correct, less specific than GO:0004709. Supporting Evidence: file:yeast/STE11/STE11-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 |
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Download this section (compressed HTML)Q: Should SGD annotations of Ste11, Ste7, Kss1 and Ste20 to GO:0001402 (signal transduction involved in filamentous growth) be migrated to the more specific GO:0062031 (filamentous growth MAPK cascade), whose definition names this kinase cascade?
Q: Is Ste11 a direct kinase for Mkk1 (Ser407/Thr411) in the Nst1-mediated crosstalk to the cell integrity pathway, or is Slt2 activation downstream of Ste11 indirect? This decides whether any cell integrity MAPK cascade annotation for Ste11 is warranted.
Q: What is the source of the Ste11 self-interaction curated from PMID:8670882 (a mammalian Rac1/POR1 paper), and does Ste11 homodimerize under physiological conditions?
Experiment: In vitro kinase assays with purified full-length Ste11 (Ste20-phosphorylated or phosphomimetic) and purified Mkk1, Ste7 and Pbs2 to test whether Mkk1 is a direct substrate and to compare kinetics across the MAPKKs.
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Download this section (compressed HTML)Signal transducing MEK kinase; involved in pheromone response and pseudohyphal/invasive growth pathways where it phosphorylates Ste7p, and the high osmolarity response pathway, via phosphorylation of Pbs2p; regulated by Ste20p and Ste50p; protein abundance increases in response to DNA replication stress
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