Ssk2 (YNR031C) is a 1579-residue STE-family serine/threonine MAP kinase kinase kinase (MAP3K) of Saccharomyces cerevisiae that, together with its paralog Ssk22, forms the MAP3K tier of the Sln1 branch of the high-osmolarity glycerol (HOG) pathway. A long N-terminal regulatory region holds the C-terminal kinase domain autoinhibited; on hyperosmotic stress the Sln1-Ypd1 phosphorelay is inhibited and unphosphorylated Ssk1 binds this region, triggering intramolecular autophosphorylation (activation-loop Thr1460) and activation. Active Ssk2 phosphorylates and activates the MAPKK Pbs2, which it recognizes through a Pbs2 N-terminal docking site that binds the Ssk2/Ssk22 kinase domain; Pbs2 then activates the p38-type MAPK Hog1. Ssk2 can also be activated independently of Ssk1 via an N-terminal segment (residues 177-240) absent from Ssk22. Ssk2 is cytosolic in unstressed cells; after osmotic shock it transiently concentrates at the bud neck (requiring the septin Shs1) and bud cortex (requiring Spa2), binds actin, and in a kinase-dependent but Ssk1- and Ssk22-independent manner promotes reassembly of the polarized actin cytoskeleton and timely cell-cycle completion. Its human homolog is MTK1/MEKK4 (MAP3K4). Independently of the HOG pathway, Ssk2 also mediates the calcium sensitivity of cells lacking the MAPK phosphatases Ptp2 and Msg5, in a mechanism that involves Msn2 and the PKA regulatory subunit Bcy1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000131 incipient cellular bud site | IDA PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: Ssk2 localizes to polarized growth sites, including the incipient bud site, in osmotically stressed cells, dependent on the polarity scaffold Spa2. Reason: SGD IDA from the Yuzyuk & Amberg 2003 localization study (abstract-only in cache; curator read the full text). Stress-induced polarized localization of Ssk2 is tied to its Ssk2-specific actin-recovery role rather than to its core Sln1-branch MAP3K function, which operates from the cytoplasm; kept as non-core. Supporting Evidence: PMID:12857882 Stress-induced localization of Ssk2p to the neck required the septin Shs1p, whereas localization to the bud cortex depended on the polarity scaffold protein Spa2p. PMID:12857882 but required a polarized distribution of Ssk2p as well as its actin-interacting and kinase activity. |
| GO:0003779 actin binding | IDA PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | KEEP AS NON CORE | Summary: Ssk2 was isolated as an actin two-hybrid interactor and forms an approximately 1:1 complex with actin after osmotic stress or latrunculin A treatment; an actin-interacting region (aa 323-1032) N-terminal to the kinase domain mediates this. Reason: Direct experimental support (two-hybrid with mapped actin-interacting region, co-precipitation with actin in stressed cells). Actin binding is required for the Ssk2-specific actin recovery function but not for canonical HOG signalling; the paralog Ssk22 lacks it. Kept as a genuine, non-core activity. Supporting Evidence: PMID:12181352 was screened, with the two-hybrid system, for actin-interacting proteins leading to the identification of the MAPKKK Ssk2p. PMID:12181352 Ssk2p concentrates in the neck of budding yeast cells and concurrently forms a 1:1 complex with actin. PMID:12181352 The role of Ssk2p in actin cytoskeleton recovery does require Ssk2p localization to the neck, its interaction with actin, and the kinase activity of Ssk2p. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based protein kinase activity; Ssk2 has a C-terminal STE-family Ser/Thr kinase domain with demonstrated catalytic activity. Reason: Correct but general; the specific activity MAP kinase kinase kinase activity (GO:0004709) is annotated experimentally. Supporting Evidence: file:yeast/SSK2/SSK2-uniprot.txt Activates the PBS2 MAP kinase kinase by phosphorylation. PMID:9482735 A conserved threonine residue (Thr1460) in the activation loop of SSK2 is important for kinase activity. |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Posas & Saito (1998) showed Ssk1-dependent activation and intramolecular autophosphorylation of Ssk2, dependence of kinase activity on activation-loop Thr1460, and (per full text) phosphorylation of Pbs2 by Ssk2 in vitro. Reason: Core molecular function. Ssk2 phosphorylates and activates the MAPKK Pbs2, and it exclusively targets Pbs2 via a Pbs2 docking site that binds the Ssk2/Ssk22 kinase domain (Tatebayashi et al. 2003). MAP kinase kinase kinase activity is the precise term, also the module MF. Supporting Evidence: PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. PMID:9482735 A conserved threonine residue (Thr1460) in the activation loop of SSK2 is important for kinase activity. PMID:7624781 Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. PMID:12853477 The Ssk2/Ssk22 MAPKKKs in the SLN1 branch, when activated, exclusively phosphorylate the Pbs2 MAPKK. file:yeast/SSK2/SSK2-deep-research-falcon.md Purified Ssk2 phosphorylated catalytically inactive Pbs2 in vitro |
| GO:0004709 MAP kinase kinase kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated MAPKKK activity from IPR017240 (MAPKKK Ssk2/Ssk22) and EC 2.7.11.25. Reason: Consistent with the experimental IDA annotation and the Ssk2/Ssk22 family assignment. Supporting Evidence: file:yeast/SSK2/SSK2-uniprot.txt Activates the PBS2 MAP kinase kinase by phosphorylation. PMID:12853477 The Ssk2/Ssk22 MAPKKKs in the SLN1 branch, when activated, exclusively phosphorylate the Pbs2 MAPKK. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: High-throughput interaction screen detected the Ssk2-Ssk1 interaction. Reason: Bare protein binding is uninformative. The partner Ssk1 is the phosphorelay response regulator whose unphosphorylated form binds the Ssk2 N-terminal regulatory domain and activates the kinase; this is a genuine and well-characterized interaction, but GO has no informative MF for binding an upstream activator, and the functional content is already carried by the MAP kinase kinase kinase activity and GO:0007234 osmosensory signaling via phosphorelay pathway annotations (the latter with SSK1 in WITH/FROM). Removing this generic row does not mean the interaction is false. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Ssk1 binds to an N-terminal regulatory domain of the Ssk2/Ssk22 MAPKKKs, as demonstrated by both two-hybrid analyses and coprecipitation assays |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: High-throughput interaction screen detected the Ssk2-Ssk1 interaction. Reason: Bare protein binding is uninformative. The partner Ssk1 is the phosphorelay response regulator whose unphosphorylated form binds the Ssk2 N-terminal regulatory domain and activates the kinase; this is a genuine and well-characterized interaction, but GO has no informative MF for binding an upstream activator, and the functional content is already carried by the MAP kinase kinase kinase activity and GO:0007234 osmosensory signaling via phosphorelay pathway annotations (the latter with SSK1 in WITH/FROM). Removing this generic row does not mean the interaction is false. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Ssk1 binds to an N-terminal regulatory domain of the Ssk2/Ssk22 MAPKKKs, as demonstrated by both two-hybrid analyses and coprecipitation assays |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: High-throughput interaction screen detected the Ssk2-Ssk1 interaction. Reason: Bare protein binding is uninformative. The partner Ssk1 is the phosphorelay response regulator whose unphosphorylated form binds the Ssk2 N-terminal regulatory domain and activates the kinase; this is a genuine and well-characterized interaction, but GO has no informative MF for binding an upstream activator, and the functional content is already carried by the MAP kinase kinase kinase activity and GO:0007234 osmosensory signaling via phosphorelay pathway annotations (the latter with SSK1 in WITH/FROM). Removing this generic row does not mean the interaction is false. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Ssk1 binds to an N-terminal regulatory domain of the Ssk2/Ssk22 MAPKKKs, as demonstrated by both two-hybrid analyses and coprecipitation assays |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: Kinase-phosphatase AP-MS network (Breitkreutz et al. 2010) detected Ssk2 with the cell wall integrity MAPK Slt2. Reason: Bare protein binding is uninformative. The Ssk2-Slt2 co-purification comes from a large AP-MS network with no follow-up; Slt2 is not a known Ssk2 substrate, regulator, or scaffold, so no informative binding MF (e.g. MAP kinase binding) can be justified from the available evidence. Removing this generic row does not mean the interaction is false. Supporting Evidence: PMID:20489023 An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: Kinase-phosphatase AP-MS network (Breitkreutz et al. 2010) detected Ssk2 with Ssk1. Reason: Bare protein binding is uninformative. The partner Ssk1 is the phosphorelay response regulator whose unphosphorylated form binds the Ssk2 N-terminal regulatory domain and activates the kinase; this is a genuine and well-characterized interaction, but GO has no informative MF for binding an upstream activator, and the functional content is already carried by the MAP kinase kinase kinase activity and GO:0007234 osmosensory signaling via phosphorelay pathway annotations (the latter with SSK1 in WITH/FROM). Removing this generic row does not mean the interaction is false. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Ssk1 binds to an N-terminal regulatory domain of the Ssk2/Ssk22 MAPKKKs, as demonstrated by both two-hybrid analyses and coprecipitation assays |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: High-throughput interaction screen detected the Ssk2-Ssk1 interaction. Reason: Bare protein binding is uninformative. The partner Ssk1 is the phosphorelay response regulator whose unphosphorylated form binds the Ssk2 N-terminal regulatory domain and activates the kinase; this is a genuine and well-characterized interaction, but GO has no informative MF for binding an upstream activator, and the functional content is already carried by the MAP kinase kinase kinase activity and GO:0007234 osmosensory signaling via phosphorelay pathway annotations (the latter with SSK1 in WITH/FROM). Removing this generic row does not mean the interaction is false. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Ssk1 binds to an N-terminal regulatory domain of the Ssk2/Ssk22 MAPKKKs, as demonstrated by both two-hybrid analyses and coprecipitation assays |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding inferred from the protein kinase ATP-binding site signatures. Reason: Ssk2 is an active ATP-dependent protein kinase (kinase-dead K1295N allele inactive), so ATP binding is correct. Supporting Evidence: file:yeast/SSK2/SSK2-uniprot.txt Activates the PBS2 MAP kinase kinase by phosphorylation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoplasm inferred from IPR017240 membership. Reason: Consistent with GFP-Ssk2 being uniformly cytoplasmic in unstressed cells (Yuzyuk et al. 2002); the MAP3K acts with cytoplasmic Ssk1 and Pbs2. Supporting Evidence: PMID:12181352 on low-osmotic medium, GFP-Ssk2p was uniformly distributed throughout the cytoplasm |
| GO:0005829 cytosol | IDA PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | ACCEPT | Summary: GFP-Ssk2 is uniformly distributed throughout the cytoplasm in unstressed cells and returns there after adaptation. Reason: Direct imaging evidence; cytosol is the resting location from which Ssk2 signals to Pbs2. Supporting Evidence: PMID:12181352 on low-osmotic medium, GFP-Ssk2p was uniformly distributed throughout the cytoplasm |
| GO:0005934 cellular bud tip | IDA PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: Ssk2 localizes to the bud cortex/bud tip in osmotically stressed cells, dependent on Spa2. Reason: SGD IDA from full text (abstract-only in cache). Transient, stress-induced polarized localization connected to the Ssk2-specific actin recovery role; non-core relative to MAP3K signalling. Supporting Evidence: PMID:12857882 Stress-induced localization of Ssk2p to the neck required the septin Shs1p, whereas localization to the bud cortex depended on the polarity scaffold protein Spa2p. PMID:12857882 but required a polarized distribution of Ssk2p as well as its actin-interacting and kinase activity. |
| GO:0005935 cellular bud neck | IDA PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | KEEP AS NON CORE | Summary: After osmotic shock or latrunculin A treatment, GFP-Ssk2 concentrates at the mother-bud neck, independently of Ssk1 and of its own kinase activity. Reason: Well-supported direct observation; the neck localization is required for Ssk2 actin recovery function, not for Pbs2 activation. Non-core. Supporting Evidence: PMID:12181352 Ssk2p concentrates in the neck of budding yeast cells and concurrently forms a 1:1 complex with actin. PMID:12181352 GFP-Ssk2p moved to the neck and cortex of small buds on application of osmotic shock |
| GO:0005935 cellular bud neck | IDA PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: Stress-induced localization of Ssk2 to the bud neck requires the septin Shs1. Reason: Consistent with PMID:12181352; transient localization related to the actin recovery role. Supporting Evidence: PMID:12857882 Stress-induced localization of Ssk2p to the neck required the septin Shs1p, whereas localization to the bud cortex depended on the polarity scaffold protein Spa2p. |
| GO:0005938 cell cortex | IDA PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | KEEP AS NON CORE | Summary: GFP-Ssk2 moves to the neck and cortex of small buds on osmotic shock. Reason: Direct imaging evidence; stress-induced cortical localization related to actin recovery. Non-core. Supporting Evidence: PMID:12181352 GFP-Ssk2p moved to the neck and cortex of small buds on application of osmotic shock |
| GO:0005938 cell cortex | IDA PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: Bud cortex localization of Ssk2 in stressed cells depends on the polarity scaffold Spa2. Reason: Consistent with PMID:12181352; related to the actin recovery role. Non-core. Supporting Evidence: PMID:12857882 Stress-induced localization of Ssk2p to the neck required the septin Shs1p, whereas localization to the bud cortex depended on the polarity scaffold protein Spa2p. PMID:12857882 Furthermore, Spa2p could be precipitated by GST-Ssk2p from extracts of osmotically stressed cells. |
| GO:0007234 osmosensory signaling via phosphorelay pathway | IGI PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Genetic interaction with SLN1 places Ssk2 downstream of the Sln1-Ypd1-Ssk1 phosphorelay osmosensor. Reason: Ssk2 is the direct output of the phosphorelay: unphosphorylated Ssk1 binds and activates it. Ssk2 performs the MAP3K step of this pathway, so the process annotation is appropriate and core. Supporting Evidence: PMID:9482735 The SSK2/SSK22 MAPKKKs are activated by a 'two-component' osmosensor composed of SLN1, YPD1 and SSK1. PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. |
| GO:0007234 osmosensory signaling via phosphorelay pathway | IGI PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Genetic interaction with SSK1 showing Ssk1-dependent activation of Ssk2. Reason: Core process; Ssk2 receives the phosphorelay signal directly from the Ssk1 response regulator. Supporting Evidence: PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. PMID:7624781 Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. |
| GO:0007234 osmosensory signaling via phosphorelay pathway | IPI PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Physical interaction of the Ssk1 receiver domain with the Ssk2 N-terminal segment. Reason: Direct physical coupling of Ssk2 to the phosphorelay output supports participation in the phosphorelay osmosensory pathway. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Ssk1 binds to an N-terminal regulatory domain of the Ssk2/Ssk22 MAPKKKs, as demonstrated by both two-hybrid analyses and coprecipitation assays |
| GO:0032956 regulation of actin cytoskeleton organization | IGI PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: Genetic interaction with SPA2: spa2 and ssk2 mutants share actin recovery defects after osmotic stress, suppressed in spa2 by overexpressed active Ssk2. Reason: SGD curator annotation supported by the abstract. Ssk2 kinase activity is required for actin recovery, so Ssk2 does part of the regulatory work (substrates unknown). This is an Ssk2-specific secondary function, independent of Ssk1 and not shared with Ssk22; kept as non-core. Supporting Evidence: PMID:12857882 spa2delta cells, like ssk2delta cells, were defective for actin recovery from osmotic stress. PMID:12857882 but required a polarized distribution of Ssk2p as well as its actin-interacting and kinase activity. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | KEEP AS NON CORE | Summary: ssk2 deletion, kinase-dead and Thr1460A alleles delay actin repolarization after osmotic stress; Ssk1 and Ssk22 are not required. Reason: Direct mutant evidence that Ssk2 (via its kinase activity, actin interaction and neck localization) promotes actin cytoskeleton reassembly. Genuine but secondary to the MAP3K role; non-core. Supporting Evidence: PMID:12181352 The role of Ssk2p in actin cytoskeleton recovery does require Ssk2p localization to the neck, its interaction with actin, and the kinase activity of Ssk2p. PMID:12181352 suggesting that Ssk2p has a specific function in actin recovery and that this function, as for localization, is not activated by Ssk1p PMID:12181352 Loss of Ssk2p, its kinase activity, or its ability to localize and interact with actin led to delays in actin recovery and a resulting delay in cell cycle completion. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: Ssk2 is required for actin recovery after osmotic stress at all cell-cycle stages, requiring its actin-interacting and kinase activities. Reason: Consistent with PMID:12181352; non-core Ssk2-specific function. Supporting Evidence: PMID:12857882 but required a polarized distribution of Ssk2p as well as its actin-interacting and kinase activity. PMID:12857882 spa2delta cells, like ssk2delta cells, were defective for actin recovery from osmotic stress. |
| GO:0038066 p38MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA placing the Ssk2/Ssk22/MEKK4-family MAP3Ks in the p38 (Hog1) MAPK cascade. Reason: GO:0038066 explicitly covers the Hog1 cascade in yeast. Ssk2 is the MAP3K tier (Ssk2/Ssk22 -> Pbs2 -> Hog1). The node includes Ssk2 itself among descendants with experimental support, which is expected, not circular. Supporting Evidence: PMID:7624781 Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. PMID:23028184 activated Ssk2/Ssk22 exclusively phosphorylates, and thereby activates, Pbs2, and activated Pbs2 phosphorylates only Hog1. |
| GO:0038066 p38MAPK cascade | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning prediction of p38MAPK cascade. Reason: Consistent with experimental evidence for Ssk2 as the MAP3K of the Hog1 cascade. Supporting Evidence: PMID:23028184 activated Ssk2/Ssk22 exclusively phosphorylates, and thereby activates, Pbs2, and activated Pbs2 phosphorylates only Hog1. |
| GO:0038066 p38MAPK cascade | IGI PMID:7624781 Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of a... | ACCEPT | Summary: Genetic interaction with SSK22: ssk2 ssk22 double mutants lose Sln1-branch activation of Pbs2. Reason: Core process. The redundancy with Ssk22 is why genetic evidence requires double mutants. Supporting Evidence: PMID:7624781 Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. |
| GO:0038066 p38MAPK cascade | IGI PMID:9742096 Requirement of STE50 for osmostress-induced activation of th... | ACCEPT | Summary: Genetic interactions of ssk2 ssk22 with ste11/ste50/sho1 show that the three MAPKKKs independently activate Pbs2 and Hog1. Reason: Core process; well supported by the full-text genetics. Supporting Evidence: PMID:9742096 Either SSK2, SSK22, or STE11 MAPKKK can activate PBS2 by phosphorylation. PMID:9742096 The three MAPKKKs (SSK2, SSK22, and STE11) can in turn independently activate the PBS2 MAPKK, the activator of the HOG1 MAPK. |
| GO:0038066 p38MAPK cascade | IMP PMID:7624781 Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of a... | ACCEPT | Summary: Mutant analysis showing Pbs2 activation by Ssk2 and Ssk22 in the Hog1 cascade. Reason: Core process, SGD experimental annotation. Supporting Evidence: PMID:7624781 Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. |
| GO:0051403 stress-activated MAPK cascade | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR017240-based stress-activated MAPK cascade. Reason: Correct: the HOG cascade is a stress-activated MAPK cascade; GO:0038066 p38MAPK cascade is the more specific description used in the experimental annotations. Supporting Evidence: PMID:23028184 activated Ssk2/Ssk22 exclusively phosphorylates, and thereby activates, Pbs2, and activated Pbs2 phosphorylates only Hog1. |
| GO:0071474 cellular hyperosmotic response | IDA PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | ACCEPT | Summary: Ssk2 relocalizes and promotes actin recovery in response to hyperosmotic shock. Reason: Ssk2 participates in the cellular hyperosmotic response both as the Sln1-branch MAP3K and in actin recovery after osmotic stress. Supporting Evidence: PMID:12181352 Ssk2p concentrates in the neck of budding yeast cells and concurrently forms a 1:1 complex with actin. PMID:12181352 Loss of Ssk2p, its kinase activity, or its ability to localize and interact with actin led to delays in actin recovery and a resulting delay in cell cycle completion. |
| GO:0071474 cellular hyperosmotic response | IDA PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Hyperosmotic treatment triggers Ssk1-dependent Ssk2 autophosphorylation and activation. Reason: Core process; Ssk2 activation is a direct response to hyperosmolarity. Supporting Evidence: PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. |
| GO:0071474 cellular hyperosmotic response | IGI PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | ACCEPT | Summary: Genetic interaction with SPA2 in recovery from osmotic stress. Reason: Ssk2 and Spa2 are both required for actin recovery after osmotic stress, part of the cellular hyperosmotic response. Supporting Evidence: PMID:12857882 spa2delta cells, like ssk2delta cells, were defective for actin recovery from osmotic stress. |
| GO:0071474 cellular hyperosmotic response | IMP PMID:12181352 The MEK kinase Ssk2p promotes actin cytoskeleton recovery af... | ACCEPT | Summary: ssk2 mutants are delayed in actin recovery and cell-cycle completion after osmotic stress. Reason: Direct mutant evidence for participation in the hyperosmotic response. Supporting Evidence: PMID:12181352 Loss of Ssk2p, its kinase activity, or its ability to localize and interact with actin led to delays in actin recovery and a resulting delay in cell cycle completion. |
| GO:0071474 cellular hyperosmotic response | IMP PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | ACCEPT | Summary: ssk2 mutants are defective for actin recovery from osmotic stress. Reason: Consistent with PMID:12181352. Supporting Evidence: PMID:12857882 spa2delta cells, like ssk2delta cells, were defective for actin recovery from osmotic stress. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based protein serine kinase activity. Reason: Correct; Ssk2 is a Ser/Thr kinase (activates Pbs2 on Ser514/Thr518 per the literature). MAP kinase kinase kinase activity is the more informative term. Supporting Evidence: file:yeast/SSK2/SSK2-uniprot.txt Activates the PBS2 MAP kinase kinase by phosphorylation. PMID:12853477 The Ssk2/Ssk22 MAPKKKs in the SLN1 branch, when activated, exclusively phosphorylate the Pbs2 MAPKK. |
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Download this section (compressed HTML)Q: What activates Ssk2 independently of Ssk1 (via N-terminal residues 177-240), both in the osmostress response and in actin recovery, and is it the same upstream input?
Q: What are the Ssk2 substrates, other than Pbs2, that mediate kinase-dependent actin cytoskeleton recovery at the bud neck and bud cortex after osmotic stress?
Q: Is Ssk2 actin binding direct (purified proteins) and does it apply to filamentous or monomeric actin?
Experiment: Analog-sensitive ssk2 allele in an ssk22 background combined with quantitative phosphoproteomics during recovery from osmotic shock, to identify Pbs2-independent Ssk2 substrates linked to actin repolarization.
Experiment: In vitro binding of purified Ssk2 actin-interacting region (aa 323-1032) to G-actin and F-actin (co-sedimentation) to test whether actin binding is direct.
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Download this section (compressed HTML)MAP kinase kinase kinase of HOG1 mitogen-activated signaling pathway; interacts with Ssk1p, leading to autophosphorylation and activation of Ssk2p which phosphorylates Pbs2p; also mediates actin cytoskeleton recovery from osmotic stress; a HOG-independent function of Ssk2p mediates the calcium-sensitive phenotype of the ptp2 msg5 double disruptant; SSK2 has a paralog, SSK22, that arose from the whole genome duplication
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