Dsor1 encodes the Drosophila MEK/MAP2K in the canonical Ras/Raf/ERK cascade. Raf-dependent activation of Dsor1 allows this dual-specificity kinase to phosphorylate and activate Rolled/ERK, transmitting EGFR, Torso, Sevenless, Pvr, FGF, and other receptor inputs to ERK-dependent developmental and stress-response outputs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference places Dsor1 in the conserved MEK/MAPKK branch of MAPK cascades. Reason: MAPK cascade is the correct high-level biological process for Dsor1, the Drosophila MEK that relays Raf-family MAPKKK activity to rolled/ERK. |
| GO:0000793 condensed chromosome | IDA PMID:17011495 An intrinsic cell cycle checkpoint pathway mediated by MEK a... | KEEP AS NON CORE | Summary: Activated Dsor1/MEK localizes to mitotic chromosomes in early embryos. Reason: The localization is experimentally supported, but mitotic chromosome association is a checkpoint-specific localization rather than the reusable Raf-to-ERK MEK activity. Supporting Evidence: PMID:17011495 The mitotic pMEK signals were found to colocalize with anaphase/telophase chromosomes |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro kinase-domain mapping is correct but too broad for Dsor1. Reason: Dsor1 is specifically the dual-specificity MAP kinase kinase in Drosophila ERK cascades; replace the generic protein kinase term with GO:0004708. Proposed replacements: MAP kinase kinase activity Supporting Evidence: file:DROME/Dsor1/Dsor1-uniprot.txt DR InterPro; IPR008271; Ser/Thr_kinase_AS. |
| GO:0004708 MAP kinase kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference captures the conserved MEK/MAPKK catalytic function of Dsor1. Reason: GO:0004708 is the core molecular function of Dsor1 and is consistent with Drosophila biochemical and genetic evidence as well as the conserved MAP2K clade. |
| GO:0004708 MAP kinase kinase activity | IDA PMID:8798773 Biochemical characterization of rolledSem, an activated form... | ACCEPT | Summary: Dsor1 directly phosphorylates and activates Drosophila rolled/ERK. Reason: In vitro assays place Dsor1 immediately upstream of rolled in the ERK cascade, supporting MAP kinase kinase activity as a core Dsor1 function. Supporting Evidence: PMID:8798773 phosphorylate and activate Rl in vitro |
| GO:0004708 MAP kinase kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The EC:2.7.12.2 IEA maps to Dsor1 MAP kinase kinase activity. Reason: UniProt records Dsor1 as EC 2.7.12.2, and the automated EC mapping lands on the specific MAP kinase kinase activity term rather than on a broader parent. Supporting Evidence: file:DROME/Dsor1/Dsor1-uniprot.txt DE EC=2.7.12.2; |
| GO:0004708 MAP kinase kinase activity | IGI PMID:9136016 Dominant mutations of Drosophila MAP kinase kinase and their... | ACCEPT | Summary: Dominant Dsor1 alleles showed activated MAP kinase kinase behavior in fly and yeast MAPK cascades. Reason: The genetic interaction with an upstream activator in a heterologous yeast MAPK cascade is consistent with Dsor1 functioning as a MAP kinase kinase. Supporting Evidence: PMID:9136016 Dsor1 can activate yeast MAP kinase homologues if a proper activator of Dsor1 is coexpressed |
| GO:0004708 MAP kinase kinase activity | IMP PMID:28166211 Divergent effects of intrinsically active MEK variants on de... | ACCEPT | Summary: Engineered Dsor1/MEK variants directly altered ERK pathway activity in vivo. Reason: The Drosophila MEK variants assayed in embryos and in vitro support Dsor1 as a MAP kinase kinase whose intrinsic activity phosphorylates downstream ERK. Supporting Evidence: PMID:28166211 intrinsically active MEK variants can both increase and reduce the levels of pathway activation in vivo |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: The RHEA tyrosine-phosphorylation mapping captures one half of Dsor1 dual specificity but is too broad by itself. Reason: Dsor1 is a dual-specificity MAP kinase kinase acting on serine/threonine and tyrosine residues of MAPK/ERK; GO:0004708 captures the integrated, substrate-specific activity better than the generic tyrosine kinase parent. Proposed replacements: MAP kinase kinase activity Supporting Evidence: file:DROME/Dsor1/Dsor1-uniprot.txt CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + |
| GO:0005515 protein binding | IPI PMID:16600911 The novel SAM domain protein Aveugle is required for Raf act... | MODIFY | Summary: The Raf-Dsor1 interaction should be captured as MAPKKK binding rather than generic protein binding. Reason: The cited assay used Raf-MEK binding as the pathway control; because Raf is the upstream MAP kinase kinase kinase for Dsor1, GO:0031435 is the informative molecular-function replacement. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:16600911 we confirmed that the C-terminal domain of Raf could interact with MEK |
| GO:0005515 protein binding | IPI PMID:18494562 Raf activation is regulated by tyrosine 510 phosphorylation ... | MODIFY | Summary: The Raf-Dsor1 interaction in the Src64B/Raf study should be curated as MAPKKK binding. Reason: The evidence reflects binding to the upstream Draf kinase that phosphorylates Dsor1/MEK; the generic GO:0005515 term should be replaced by GO:0031435. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:18494562 using protein extracts and in vitro kinase assays with the downstream suppressor of Raf 1 (Dsor1; a MEK homolog) as substrate |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is expected for the Dsor1 protein kinase domain. Reason: Dsor1 is an ATP-dependent MAP kinase kinase and carries a protein kinase ATP-binding site, so this broad molecular-function term is acceptable. Supporting Evidence: file:DROME/Dsor1/Dsor1-uniprot.txt DR InterPro; IPR017441; Protein_kinase_ATP_BS. |
| GO:0005635 nuclear envelope | IDA PMID:17011495 An intrinsic cell cycle checkpoint pathway mediated by MEK a... | KEEP AS NON CORE | Summary: Activated Dsor1/MEK concentrates at the nuclear envelope at the G2/M transition. Reason: The nuclear-envelope colocalization is direct but specific to cell-cycle checkpoint activation rather than a constitutive core localization of the MEK module. Supporting Evidence: PMID:17011495 The late interphase pMEK signals were found more concentrated on the nuclear envelope |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: A cytoplasmic annotation is biologically compatible with Dsor1/MEK signaling. Reason: Dsor1 is a cytoplasmic signaling kinase in Ras/Raf/MEK/ERK cascades, and the ARBA cytoplasm inference is consistent with that localization. |
| GO:0005829 cytosol | TAS Reactome:R-DME-209196 | REMOVE | Summary: The Reactome event is a PKA-C1 Hedgehog reaction, not a Dsor1 reaction. Reason: This TAS row appears to come from a Drosophila Reactome event whose enabled kinase is PKA-C1 phosphorylating Cubitus interruptus, so it does not support Dsor1 cytosol localization. Supporting Evidence: Reactome:R-DME-209196 Cubitus Interruptus (CI) is primed for phosphorylation by Protein kinase A (PKA-C1) |
| GO:0005829 cytosol | TAS Reactome:R-DME-209341 | REMOVE | Summary: The Reactome event is a PKA-C1 Smoothened phosphorylation reaction, not a Dsor1 reaction. Reason: This event describes Protein kinase A acting on Smoothened in the Hedgehog pathway and is not evidence for Dsor1. Supporting Evidence: Reactome:R-DME-209341 Protein kinase A (PKA-C1) carries out priming phosphorylation of the transmembrane protein Smoothened |
| GO:0005829 cytosol | TAS Reactome:R-DME-432535 | REMOVE | Summary: The Reactome event is a CK2-Timeless phosphorylation reaction, not a Dsor1 reaction. Reason: Casein kinase II, not Dsor1/MEK, is the kinase in this circadian Reactome event. Supporting Evidence: Reactome:R-DME-432535 Timeless (TIM) is phosphorylated on unknown serine/threonine residues by casein kinase II (CK2). |
| GO:0005829 cytosol | TAS Reactome:R-DME-432590 | REMOVE | Summary: The Reactome event is a CK2-Period phosphorylation reaction, not a Dsor1 reaction. Reason: Casein kinase II, not Dsor1/MEK, is the kinase in this Period phosphorylation event. Supporting Evidence: Reactome:R-DME-432590 Phosphorylated Period (PER) is phosphorylated on serine residues 149, 151, 153, by casein kinase II (CK2). |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:17011495 An intrinsic cell cycle checkpoint pathway mediated by MEK a... | KEEP AS NON CORE | Summary: Dsor1/MEK is required for DNA-damage-induced checkpoint arrest in early embryos. Reason: The checkpoint role is experimentally supported, but it is a Drosophila early-embryo cell-cycle output of MEK/ERK rather than the core MAP kinase kinase activity itself. Supporting Evidence: PMID:17011495 MEK/ERK activation is required for multiple checkpoints and is essential for orderly cell cycle progression |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:7958887 A temperature-sensitive MEK mutation demonstrates the conser... | KEEP AS NON CORE | Summary: Temperature-sensitive D-Mek experiments support Dsor1 in the Drosophila EGFR pathway. Reason: Dsor1 is the common MEK downstream of multiple fly RTKs; EGFR signaling is a real context for Dsor1 activity but is receptor-specific. Supporting Evidence: PMID:7958887 D-Mek operates in the Sevenless and in the Drosophila epidermal growth factor RTK pathways |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:9136016 Dominant mutations of Drosophila MAP kinase kinase and their... | KEEP AS NON CORE | Summary: Dominant Dsor1 alleles genetically interacted with DER/EGFR among several RTK pathways. Reason: The row is consistent with Dsor1 as the shared MEK in RTK pathways, but EGFR signaling is one receptor-specific deployment of the core kinase. Supporting Evidence: PMID:9136016 They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER) |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:21683597 Phosphorylation of Groucho mediates RTK feedback inhibition ... | KEEP AS NON CORE | Summary: RTK-to-MAPK signaling through Dsor1 relieves Groucho-mediated repression in Drosophila embryos. Reason: The paper supports a general RTK/MAPK output in multiple developmental contexts; the EGFR pathway assertion is plausible but receptor-specific rather than Dsor1 core biology. Supporting Evidence: PMID:21683597 RTK pathways use Groucho phosphorylation as a general mechanism for inducing expression of pathway target genes |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:22242005 MAPK/ERK signaling regulates insulin sensitivity to control ... | KEEP AS NON CORE | Summary: EGFR-regulated MAPK/ERK signaling through Raf and D-MEK modulates insulin receptor expression. Reason: The data connect Dsor1/D-MEK to EGFR-regulated ERK output in metabolic control, a context-specific branch of its shared MEK activity. Supporting Evidence: PMID:22242005 we silenced the expression of Raf and D-MEK, which also showed reduced InR expression |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:7958887 A temperature-sensitive MEK mutation demonstrates the conser... | KEEP AS NON CORE | Summary: D-Mek acts in the Drosophila EGFR pathway. Reason: This is a supported RTK-specific process annotation for Dsor1, but the core reusable function is MAP kinase kinase activity in the Raf/MEK/ERK cassette. Supporting Evidence: PMID:7958887 D-Mek operates in the Sevenless and in the Drosophila epidermal growth factor RTK pathways |
| GO:0007298 border follicle cell migration | IGI PMID:17637670 Two distinct modes of guidance signalling during collective ... | KEEP AS NON CORE | Summary: MAPK signaling contributes to the later phase of border-cell migration. Reason: Border-cell migration is a PVR/EGFR developmental output that uses MAPK, but it is not the core molecular role of Dsor1. Supporting Evidence: PMID:17637670 During the later phase, mitogen-activated protein kinase and phospholipase Cgamma are used redundantly |
| GO:0007362 terminal region determination | IMP PMID:10652276 Relief of gene repression by torso RTK signaling: role of ca... | KEEP AS NON CORE | Summary: Terminal patterning is a Torso-to-Ras/Raf/MAPK output. Reason: Dsor1 functions in the Torso MAPK pathway, but terminal region determination is a maternal embryonic developmental output rather than the core kinase function. Supporting Evidence: PMID:10652276 Tor signaling proceeds via the Ras/Raf/MAPK pathway to regulate expression of the zygotic genes tailless |
| GO:0007362 terminal region determination | IMP PMID:28166211 Divergent effects of intrinsically active MEK variants on de... | KEEP AS NON CORE | Summary: Engineered Dsor1/MEK variants perturb Torso-dependent terminal signaling in the early embryo. Reason: The experiment directly used Drosophila Dsor1 variants in the early Torso patterning system; the terminal-patterning term is valid but non-core. Supporting Evidence: PMID:28166211 ERK activation is triggered by a locally produced ligand (Trunk) via a uniformly expressed RTK (Torso) |
| GO:0007430 terminal branching, open tracheal system | IMP PMID:25061859 Slik and the receptor tyrosine kinase Breathless mediate loc... | KEEP AS NON CORE | Summary: Dsor1/MEK is required for terminal tracheal-cell branching downstream of the Breathless FGFR pathway. Reason: The paper separates Breathless-dependent Moesin phosphorylation from the MAPK cascade but still shows that Mek knockdown reduces terminal cell branching, so this developmental output can be kept as non-core. Supporting Evidence: PMID:25061859 Knockdown of each of the components caused a reduction in the number of terminal cell branches |
| GO:0007465 R7 cell fate commitment | IGI PMID:8722784 A screen for genes that function downstream of Ras1 during D... | KEEP AS NON CORE | Summary: Dsor1 was recovered genetically as a downstream Ras/MAPK factor in R7 photoreceptor fate. Reason: R7 fate commitment is a Sevenless/EGFR eye-development output of the Ras/Raf/MEK/MAPK module, not the central catalytic function of Dsor1. Supporting Evidence: PMID:8722784 Mutations in the Drosophila homologues of Raf, MEK, MAPK |
| GO:0007465 R7 cell fate commitment | IMP PMID:7958887 A temperature-sensitive MEK mutation demonstrates the conser... | KEEP AS NON CORE | Summary: Temperature-sensitive D-Mek experiments demonstrate a requirement for Dsor1 in photoreceptor RTK signaling. Reason: Photoreceptor fate is a developmental output of Sevenless and EGFR signaling through Dsor1, so it should be retained as non-core. Supporting Evidence: PMID:7958887 D-Mek operates in the Sevenless and in the Drosophila epidermal growth factor RTK pathways |
| GO:0008286 insulin receptor signaling pathway | IDA PMID:10823906 Use of double-stranded RNA interference in Drosophila cell l... | KEEP AS NON CORE | Summary: Dsor1 RNAi blocks insulin-induced activation of downstream ERK-A in Drosophila cells. Reason: Dsor1 can relay insulin-stimulated signals to ERK-A, but insulin signaling is one receptor context for the shared MEK activity. Supporting Evidence: PMID:10823906 inhibiting the expression of the DSOR1 (mitogen-activated protein kinase kinase, MAPKK) prevents the activation of the downstream ERK-A |
| GO:0008286 insulin receptor signaling pathway | IDA PMID:15337530 Drosophila PI3 kinase and Akt involved in insulin-stimulated... | KEEP AS NON CORE | Summary: Insulin activates dMEK and dERK in Schneider cells as part of a proliferative ERK output. Reason: The row captures a real insulin-stimulated ERK pathway context for Dsor1, but not its core kinase activity. Supporting Evidence: PMID:15337530 After insulin treatment, dPI3K and dAKT activities were both increased along with activation of the dERK pathway components dMEK and dERK |
| GO:0008286 insulin receptor signaling pathway | IDA PMID:23980175 ERK signaling couples nutrient status to antiviral defense i... | KEEP AS NON CORE | Summary: Insulin-linked ERK signaling has an antiviral output in insect gut cells. Reason: The cached abstract supports insulin-responsive ERK antiviral signaling but does not expose the Dsor1-specific assay, so this receptor-context row is retained as a plausible non-core MAPK output rather than promoted to core. Supporting Evidence: PMID:23980175 vertebrate insulin, which activates ERK in the mosquito gut during a blood meal, restricts viral infection in Drosophila cells |
| GO:0008286 insulin receptor signaling pathway | IDA PMID:26119340 The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longe... | KEEP AS NON CORE | Summary: Ras-Erk signaling acts downstream of insulin/IGF-like signaling in Drosophila lifespan control. Reason: The insulin receptor context is supported as a physiological Ras-Erk output, but lifespan/metabolic regulation is not the reusable Dsor1 molecular function. Supporting Evidence: PMID:26119340 attenuation of Ras-Erk-ETS signaling is implicated in the effects of reduced IIS on aging |
| GO:0008293 torso signaling pathway | IGI PMID:10511556 Genetic analysis of rolled, which encodes a Drosophila mitog... | KEEP AS NON CORE | Summary: rolled genetics place Dsor1 in the Torso signaling pathway. Reason: Torso signaling is a receptor-specific early-embryo deployment of the core MEK/ERK cascade. Supporting Evidence: PMID:10511556 activation of Rl is essential, but not sufficient, for Tor signaling |
| GO:0008293 torso signaling pathway | IGI PMID:8381718 A protein kinase similar to MAP kinase activator acts downst... | KEEP AS NON CORE | Summary: Dsor1 was originally identified genetically downstream of D-raf in terminal class/Torso signaling. Reason: The genetic evidence supports Dsor1 in Torso signaling; the receptor-specific process is non-core relative to the central MAPKK activity. Supporting Evidence: PMID:8381718 Dsor1, a putative factor downstream of D-raf, was genetically identified by screening of dominant suppressors of D-raf |
| GO:0008293 torso signaling pathway | IGI PMID:9136016 Dominant mutations of Drosophila MAP kinase kinase and their... | KEEP AS NON CORE | Summary: Dominant Dsor1 alleles suppress torso mutations among several RTK pathways. Reason: The torso pathway row is correct for Dsor1 but context-specific. Supporting Evidence: PMID:9136016 They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER) |
| GO:0008293 torso signaling pathway | IMP PMID:28166211 Divergent effects of intrinsically active MEK variants on de... | KEEP AS NON CORE | Summary: Intrinsically active Dsor1/MEK variants alter the Torso-dependent ERK pattern in blastoderm embryos. Reason: This is a supported Torso-pathway perturbation but remains a receptor/developmental context of Dsor1 MEK activity. Supporting Evidence: PMID:28166211 ERK activation is triggered by a locally produced ligand (Trunk) via a uniformly expressed RTK (Torso) |
| GO:0008340 determination of adult lifespan | IMP PMID:26119340 The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longe... | KEEP AS NON CORE | Summary: Reduced Ras-Erk signaling is sufficient to increase adult lifespan. Reason: Adult lifespan is a physiological output of Ras-Erk-ETS attenuation rather than the core kinase activity that Dsor1 executes. Supporting Evidence: PMID:26119340 direct reduction of Ras or Erk activity leads to increased lifespan. |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IMP PMID:15634694 FGF signalling and the mechanism of mesoderm spreading in Dr... | KEEP AS NON CORE | Summary: Heartless/FGFR activates MAPK in mesodermal cells. Reason: The FGFR pathway is a real RTK context for the Ras/Raf/MEK/MAPK cassette; it should be retained as non-core for Dsor1. Supporting Evidence: PMID:15634694 triggers the di-phosphorylation of MAPK in the mesoderm |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IMP PMID:25061859 Slik and the receptor tyrosine kinase Breathless mediate loc... | KEEP AS NON CORE | Summary: The Breathless FGFR uses the Ras/Raf/Mek/Erk cascade during terminal tracheal development. Reason: Mek knockdown reduced terminal branching downstream of Breathless/FGFR signaling, so the pathway row is kept as a context-specific output. Supporting Evidence: PMID:25061859 Knockdown of each of the components caused a reduction in the number of terminal cell branches |
| GO:0009953 dorsal/ventral pattern formation | IGI PMID:7958887 A temperature-sensitive MEK mutation demonstrates the conser... | KEEP AS NON CORE | Summary: Dorsal/ventral patterning is affected by D-Mek activity through RTK/MAPK developmental signaling. Reason: The row reflects an early embryonic patterning consequence of Dsor1 in RTK cascades and is non-core. Supporting Evidence: PMID:7958887 different RTK pathways respond differently to alteration in D-Mek activity |
| GO:0019900 kinase binding | IPI PMID:29433126 MEK drives BRAF activation through allosteric control of KSR... | MODIFY | Summary: Dsor1 binds both Raf and KSR proteins in the ERK module. Reason: GO:0019900 is correct but broad; the interaction evidence is better split into binding to the upstream MAPKKK Raf and binding to the KSR scaffold that organizes Raf/MEK/ERK signaling. Proposed replacements: mitogen-activated protein kinase kinase kinase binding scaffold protein binding Supporting Evidence: PMID:29433126 Transactivation of Drosophila RAF (dRAF) by Drosophila KSR (dKSR) requires MEK binding |
| GO:0033314 mitotic DNA replication checkpoint signaling | IMP PMID:17011495 An intrinsic cell cycle checkpoint pathway mediated by MEK a... | KEEP AS NON CORE | Summary: Dsor1/MEK is required for the intrinsic DNA-replication checkpoint in Drosophila embryos. Reason: The checkpoint evidence is strong but represents a specialized early-cell-cycle role of the MEK/ERK pathway. Supporting Evidence: PMID:17011495 MEK is required for normal MBT and the DNA replication checkpoint |
| GO:0042386 hemocyte differentiation | IGI PMID:11919715 The Hopscotch Jak kinase requires the Raf pathway to promote... | KEEP AS NON CORE | Summary: The Hopscotch blood-cell activation phenotype requires the Raf/MEK/ERK arm. Reason: Hemocyte differentiation is a JAK/Raf pathway output in larval blood cells, not the central Dsor1 molecular activity. Supporting Evidence: PMID:11919715 Hop requires the activity of the Raf pathway to promote the activation response of larval plasmatocytes |
| GO:0042461 photoreceptor cell development | IGI PMID:8033205 The activities of two Ets-related transcription factors requ... | KEEP AS NON CORE | Summary: Ras/MAPK signaling regulates ETS transcription factors during Drosophila eye development. Reason: Photoreceptor development is a downstream developmental outcome of the Dsor1-dependent MAPK cascade. Supporting Evidence: PMID:8033205 The pointed gene codes for two related proteins |
| GO:0045500 sevenless signaling pathway | IGI PMID:8722784 A screen for genes that function downstream of Ras1 during D... | KEEP AS NON CORE | Summary: Dsor1 functions downstream of Ras in Sevenless-controlled R7 photoreceptor development. Reason: Sevenless signaling is a receptor-specific deployment of the Raf/MEK/ERK cassette. Supporting Evidence: PMID:8722784 Cell-fate specification of the R7 photoreceptor cell is controlled by the sevenless receptor tyrosine kinase |
| GO:0045500 sevenless signaling pathway | IGI PMID:9136016 Dominant mutations of Drosophila MAP kinase kinase and their... | KEEP AS NON CORE | Summary: Dominant Dsor1 alleles genetically interact with Sevenless signaling. Reason: The Sevenless row is consistent with Dsor1 function in fly RTK pathways but is not the reusable core MEK function. Supporting Evidence: PMID:9136016 They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER) |
| GO:0045500 sevenless signaling pathway | IMP PMID:7958887 A temperature-sensitive MEK mutation demonstrates the conser... | KEEP AS NON CORE | Summary: Temperature-sensitive D-Mek experiments support Dsor1 in Sevenless signaling. Reason: Sevenless-mediated R7 specification is a non-core receptor-specific output of Dsor1 MEK activity. Supporting Evidence: PMID:7958887 D-Mek operates in the Sevenless and in the Drosophila epidermal growth factor RTK pathways |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:25130174 Switching between humoral and cellular immune responses in D... | KEEP AS NON CORE | Summary: GBP/Pvr signaling uses ERK in Drosophila hemocyte-like cells. Reason: Pvr is a PDGF/VEGF receptor homolog that can recruit ERK during immune-cell state switching; this is a context-specific RTK output of Dsor1. Supporting Evidence: PMID:25130174 Activated Pvr recruits extracellular signal-regulated protein kinase to inhibit humoral immune responses |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:21297578 Drosophila Ras/MAPK signalling regulates innate immune respo... | KEEP AS NON CORE | Summary: The Ras/MAPK innate-immune paper supports receptor-to-Ras/MAPK immune regulation. Reason: The cached abstract does not expose a direct Dsor1/Pvr experiment from this paper, but the Pvr-to-ERK pathway is supported by adjacent hemocyte evidence; retain the row as a non-core immune-cell RTK/MAPK context. Supporting Evidence: PMID:21297578 we identified components of the Ras/MAPK pathway as essential for suppression of IMD pathway activity |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:25749252 A systems-level interrogation identifies regulators of Droso... | KEEP AS NON CORE | Summary: Pvr activates Ras/Erk survival and proliferation signaling in Drosophila blood cells. Reason: The VEGF/Pvr pathway is a hemocyte-specific receptor input into Ras/Erk signaling and should be kept as a non-core Dsor1 process. Supporting Evidence: PMID:25749252 the ability of Pvr to activate Ras/Erk, Akt/TOR, and yet-uncharacterized signaling pathway/s |
| GO:0051607 defense response to virus | IMP PMID:23980175 ERK signaling couples nutrient status to antiviral defense i... | KEEP AS NON CORE | Summary: ERK signaling restricts antiviral infection in the insect gut. Reason: The antiviral gut barrier is a physiological output of ERK signaling rather than the conserved core MEK catalytic function. Supporting Evidence: PMID:23980175 the nutrient responsive ERK pathway is both induced by and restricts disparate arboviruses in Drosophila intestines |
| GO:0070371 ERK1 and ERK2 cascade | HGI PMID:24643257 A functional screen reveals an extensive layer of transcript... | ACCEPT | Summary: Genome-wide epistasis screening recovered Dsor1 as a core Ras/MAPK component upstream of MAPK. Reason: The HGI screen specifically positioned mek/Dsor1 in the Ras-to-MAPK cascade, supporting the core ERK cascade process. Supporting Evidence: PMID:24643257 raf/phl, mek/Dsor1, mapk/rl, cnk, and ksr |
| GO:0070371 ERK1 and ERK2 cascade | IDA PMID:11850406 KSR is a scaffold required for activation of the ERK/MAPK mo... | ACCEPT | Summary: KSR-dependent Raf/MEK work places Dsor1 in the ERK/MAPK module. Reason: The ERK cascade is Dsor1 core biology; KSR facilitates Raf phosphorylation of MEK in this module. Supporting Evidence: PMID:11850406 we found that KSR facilitates the phosphorylation of MEK by RAF |
| GO:0070371 ERK1 and ERK2 cascade | IDA PMID:16600912 A KSR/CNK complex mediated by HYP, a novel SAM domain-contai... | ACCEPT | Summary: KSR/CNK/HYP experiments support Ras-dependent Raf activation upstream of Dsor1 and ERK. Reason: The evidence concerns assembly and regulation of the Ras/Raf/MEK/ERK module in which Dsor1 is the MEK step. Supporting Evidence: PMID:16600912 RAF is a critical effector of the small GTPase RAS |
| GO:0070371 ERK1 and ERK2 cascade | IDA PMID:29433126 MEK drives BRAF activation through allosteric control of KSR... | ACCEPT | Summary: MEK binding to KSR allosterically controls Raf-family activation in the ERK module. Reason: The work explicitly extends the KSR/RAF/MEK mechanism to the Drosophila proteins and supports Dsor1 in the ERK cascade. Supporting Evidence: PMID:29433126 Transactivation of Drosophila RAF (dRAF) by Drosophila KSR (dKSR) requires MEK binding |
| GO:0070371 ERK1 and ERK2 cascade | IDA PMID:8798773 Biochemical characterization of rolledSem, an activated form... | ACCEPT | Summary: Dsor1 phosphorylates and activates Drosophila rolled/ERK. Reason: Direct activation of rolled by Dsor1 is the defining kinase step in the Drosophila ERK cascade. Supporting Evidence: PMID:8798773 phosphorylate and activate Rl in vitro |
| GO:0070371 ERK1 and ERK2 cascade | IGI PMID:10823906 Use of double-stranded RNA interference in Drosophila cell l... | ACCEPT | Summary: Dsor1 RNAi prevents insulin-induced activation of downstream ERK-A. Reason: Although the evidence is from insulin stimulation, the asserted ERK cascade term is the correct core pathway module for Dsor1. Supporting Evidence: PMID:10823906 inhibiting the expression of the DSOR1 (mitogen-activated protein kinase kinase, MAPKK) prevents the activation of the downstream ERK-A |
| GO:0070371 ERK1 and ERK2 cascade | IMP PMID:28166211 Divergent effects of intrinsically active MEK variants on de... | ACCEPT | Summary: Intrinsically active Drosophila Dsor1 variants alter ERK phosphorylation in vivo. Reason: The row asserts the generic ERK cascade, which is the core pathway that Dsor1 controls downstream of Ras/Raf. Supporting Evidence: PMID:28166211 intrinsically active MEK variants can both increase and reduce the levels of pathway activation in vivo |
| GO:0071481 cellular response to X-ray | IMP PMID:17011495 An intrinsic cell cycle checkpoint pathway mediated by MEK a... | KEEP AS NON CORE | Summary: Dsor1/MEK is required for the embryonic X-ray checkpoint response. Reason: The DNA-damage response is supported but represents a stress/checkpoint deployment of the MEK/ERK pathway rather than Dsor1 core signaling. Supporting Evidence: PMID:17011495 The MEK/ERK checkpoint pathway is also essential to mediate an extrinsic pathway, halting cell cycle progression in response to ionizing radiation |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: The RHEA serine-phosphorylation mapping captures part of Dsor1 chemistry but is less specific than MAPKK activity. Reason: Dsor1 performs dual-specificity phosphorylation of ERK/MAPK; GO:0004708 is more informative than the generic protein serine kinase parent. Proposed replacements: MAP kinase kinase activity Supporting Evidence: file:DROME/Dsor1/Dsor1-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] |
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Download this section (compressed HTML)Downstream of raf1 (Dsor1) encodes a serine/threonine kinase that phosphorylates MAP kinase. It is activated by the product of Raf and acts downstream of receptor tyrosine kinases such as those encoded by tor, Egfr, and sev.
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