EGFR signaling pathway in Drosophila melanogaster

Drosophila has a single EGF receptor (Egfr), a receptor tyrosine kinase activated by the TGF-alpha-like ligands Spitz, Keren and Gurken and the neuregulin-like ligand Vein. Spitz, Keren and Gurken are made as inactive membrane-bound precursors; the chaperone Star carries them from the endoplasmic reticulum to the Golgi, where rhomboid intramembrane proteases cleave them to release the secreted ligand. Ligand-bound Egfr recruits the adaptor Drk (Grb2) and the guanine nucleotide exchange factor Son of sevenless, which activates Ras85D. Ras triggers the Raf, Dsor1 (MEK) and Rolled (ERK) kinase cascade, assisted by the scaffolds KSR, CNK and Aveugle. ERK changes nuclear gene expression by activating the ETS factor Pointed and promoting the degradation or export of the repressors Yan (Aop) and Capicua. The pathway acts in oogenesis axis formation, photoreceptor recruitment, wing vein formation, and cell survival and proliferation in many tissues.

MODULE:dmel_egfr_signalingDRAFTCONCRETESignaling Pathwaymodules/dmel_egfr_signaling.yaml

epidermal growth factor receptor signaling pathwayGO:0007173

FB:FBgg0000958

FlyBase gene group EGFR-RTK: Egfr signaling pathway

FlyBase release FB2026_03 groups 83 D. melanogaster genes as egfr signaling pathway (EGFR-RTK); this module models that group.

GO:0007173

epidermal growth factor receptor signaling pathway

GO term grounding the module as epidermal growth factor receptor signaling pathway.

Boundary. Core components (FlyBase EGFR-C) and ligand production (EGF-PRO). The Ras-MAPK cascade, adaptors and ETS outputs are shared with FGFR, Sevenless and Torso signaling. Feedback inhibitors (Argos, Sprouty, Kekkon1) and other FlyBase regulators are not parts. Protease activity is asserted only for the rhomboids whose ligand cleavage is well established (Rho, Roughoid, Stet). FlyBase groups realized by this module: EGFR-RTK (FBgg0000958). Subgroups folded into it: EGFR-C, EGF-PRO. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: EGFR-N (negative regulators of egfr signaling pathway, 38 genes); EGFR-P (positive regulators of egfr signaling pathway, 17 genes). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_egfr_signaling.yaml. Member genes with a gene review in this repository: drk, Dsor1, Egfr, Raf, Ras85D, rasp, rl, Sos, spi.

8Nodes

7Parts

0Variant Sets

0Variants

31Annotons

6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_egfr_signaling deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

6 gene-function check(s) reflected in core functions · 0 conflict(s) · 13 evidence or coverage gap(s) (19 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
egfr_ligand_production_rho	rho UniProtKB:P20350 Gene	serine-type endopeptidase activity GO:0004252	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_ligand_production_ru	ru UniProtKB:Q9W0F8 Gene	serine-type endopeptidase activity GO:0004252	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_ligand_production_stet	stet UniProtKB:Q9W0E9 Gene	serine-type endopeptidase activity GO:0004252	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_ligands_spi	spi UniProtKB:Q01083 Gene	growth factor activity GO:0008083	Function Unreviewed No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
egfr_ligands_krn	Krn UniProtKB:Q9VVJ6 Gene	growth factor activity GO:0008083	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_ligands_grk	grk UniProtKB:P42287 Gene	growth factor activity GO:0008083	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_ligands_vn	vn UniProtKB:Q94918 Gene	growth factor activity GO:0008083	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_receptor_egfr	Egfr UniProtKB:P04412 Gene	epidermal growth factor receptor activity GO:0005006	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
egfr_adaptors_and_ras_activation_csw	csw UniProtKB:P29349 Gene	protein tyrosine phosphatase activity GO:0004725	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_adaptors_and_ras_activation_sos	Sos UniProtKB:P26675 Gene	guanyl-nucleotide exchange factor activity GO:0005085	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
egfr_ras_ras85d	Ras85D UniProtKB:P08646 Gene	GTPase activity GO:0003924	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
egfr_mapk_cascade_raf	Raf UniProtKB:P11346 Gene	MAP kinase kinase kinase activity GO:0004709	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
egfr_mapk_cascade_dsor1	Dsor1 UniProtKB:Q24324 Gene	MAP kinase kinase activity GO:0004708	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
egfr_mapk_cascade_rl	rl UniProtKB:P40417 Gene	MAP kinase activity GO:0004707	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
egfr_nuclear_output_pnt	pnt UniProtKB:P51023 Gene	DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_nuclear_output_aop	aop UniProtKB:Q01842 Gene	DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_nuclear_output_cic	cic UniProtKB:Q9U1H0 Gene	DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_nuclear_output_gro	gro UniProtKB:P16371 Gene	transcription corepressor activity GO:0003714	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
egfr_nuclear_output_ttk	ttk UniProtKB:P42282 Gene	DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.

Gene-review completeness (10/31 grounded genes reviewed)

4 complete review(s) · 9 with deep research · 21 missing review · 1 reviewed but lacking deep research

Gene	Review	Complete	Deep research
cnk A1ZAS2	✗	—	—
drk Q08012	✓	74/76	✓
Dsor1 Q24324	✓	✓	✓
Egfr P04412	✓	137/141	✓
gro P16371	✗	—	—
rho P20350	✗	—	—
csw P29349	✗	—	—
ttk P42282	✗	—	—
grk P42287	✗	—	—
S P42519	✗	—	—
pnt P51023	✗	—	—
aop Q01842	✗	—	—
ksr Q24171	✗	—	—
phyl Q27934	✗	—	—
ave Q8ML92	✗	—	—
vn Q94918	✗	—	—
ebi Q95RJ9	✗	—	—
Vav Q9NHV9	✗	—	—
cic Q9U1H0	✗	—	—
Shc Q9V3C8	✗	—	—
Krn Q9VVJ6	✗	—	—
rho-4 Q9VYW6	✗	—	—
stet Q9W0E9	✗	—	—
ru Q9W0F8	✗	—	—
Raf P11346	✓	89/90	✓
Ras85D P08646	✓	✓	✓
rasp Q9VZU2	✓	✓	✓
rl P40417	✓	119/125	✓
Sos P26675	✓	47/50	✗
spi Q01083	✓	63/65	✓
Zpr1 Q9W379	✓	✓	✓

Tree

EGFR signalingSignaling Pathwaydmel_egfr_signaling

Parts
1. 1. ligand trafficking and processing
2. EGFR ligand productionSignaling Pathwayegfr_ligand_production
  
  Annotons
  - S EGFR ligand production Gene Product: S
  - rasp EGFR ligand production Gene Product: rasp
  - rho EGFR ligand production Gene Product: rho
  - rho-4 EGFR ligand production Gene Product: rho-4
  - ru EGFR ligand production Gene Product: ru
  - stet EGFR ligand production Gene Product: stet
3. 2. secreted ligands
4. EGFR ligandsSignaling Pathwayegfr_ligands
  
  Annotons
  - spi EGFR ligands Gene Product: spi
  - Krn EGFR ligands Gene Product: Krn
  - grk EGFR ligands Gene Product: grk
  - vn EGFR ligands Gene Product: vn
5. 3. receptor tyrosine kinase
6. EgfrSignaling Pathwayegfr_receptor
  
  Annotons
  - Egfr Egfr Gene Product: Egfr
7. 4. phosphotyrosine adaptors, phosphatase and exchange factors
8. Receptor adaptors and Ras activationSignaling Pathwayegfr_adaptors_and_ras_activation
  
  Annotons
  - drk Receptor adaptors and Ras activation Gene Product: drk
  - Shc Receptor adaptors and Ras activation Gene Product: Shc
  - csw Receptor adaptors and Ras activation Gene Product: csw
  - Sos Receptor adaptors and Ras activation Gene Product: Sos
  - Vav Receptor adaptors and Ras activation Gene Product: Vav
9. 5. small GTPase switch
10. Ras85DSignaling Pathwayegfr_ras
  
  Annotons
  - Ras85D Ras85D Gene Product: Ras85D
11. 6. kinase cascade and scaffolds
12. Raf-Dsor1-Rolled MAP kinase cascadeSignaling Pathwayegfr_mapk_cascade
  
  Annotons
  - Raf Raf-Dsor1-Rolled MAP kinase cascade Gene Product: Raf
  - Dsor1 Raf-Dsor1-Rolled MAP kinase cascade Gene Product: Dsor1
  - rl Raf-Dsor1-Rolled MAP kinase cascade Gene Product: rl
  - ksr Raf-Dsor1-Rolled MAP kinase cascade Gene Product: ksr
  - cnk Raf-Dsor1-Rolled MAP kinase cascade Gene Product: cnk
  - ave Raf-Dsor1-Rolled MAP kinase cascade Gene Product: ave
13. 7. transcription factors and co-repressor turnover
14. Nuclear transcriptional outputSignaling Pathwayegfr_nuclear_output
  
  Annotons
  - pnt Nuclear transcriptional output Gene Product: pnt
  - aop Nuclear transcriptional output Gene Product: aop
  - cic Nuclear transcriptional output Gene Product: cic
  - gro Nuclear transcriptional output Gene Product: gro
  - ttk Nuclear transcriptional output Gene Product: ttk
  - phyl Nuclear transcriptional output Gene Product: phyl
  - ebi Nuclear transcriptional output Gene Product: ebi
  - Zpr1 Nuclear transcriptional output Gene Product: Zpr1

Details

Context

Drosophila melanogasterNCBITaxon:7227

EGFR signalingSignaling Pathwaydmel_egfr_signaling

Rhomboid-processed EGF ligands activate Egfr, which signals through Drk, Sos, Ras and the Raf-Dsor1-Rolled cascade to control ETS and Capicua transcriptional outputs.

epidermal growth factor receptor signaling pathwayGO:0007173

Context

Drosophila melanogasterNCBITaxon:7227

Connections

egfr_ligand_production -> egfr_ligands Provides Input For

Star trafficking and rhomboid cleavage release active Spitz, Keren and Gurken.

egfr_ligands -> egfr_receptor Positively Regulates

Ligand binding induces Egfr dimerization and autophosphorylation.

egfr_receptor -> egfr_adaptors_and_ras_activation Positively Regulates

Phosphorylated Egfr recruits Drk/Shc and Sos.

egfr_adaptors_and_ras_activation -> egfr_ras Positively Regulates

Sos catalyses GDP-GTP exchange on Ras85D.

egfr_ras -> egfr_mapk_cascade Positively Regulates

GTP-bound Ras activates Raf.

egfr_mapk_cascade -> egfr_nuclear_output Positively Regulates

Rolled (ERK) phosphorylates Pointed, Yan and Capicua to change target gene transcription.

Part 1: ligand trafficking and processing

EGFR ligand productionSignaling Pathwayegfr_ligand_production

Star escorts ligand precursors from the ER to the Golgi; the rhomboid proteases Rhomboid, Roughoid (Rhomboid-3), Stem cell tumor (Rhomboid-2) and Rhomboid-4 cleave them; Rasp N-palmitoylates Spitz.

Annotons

S EGFR ligand production

egfr_ligand_production_s

Participant: Gene Product: S

Gene Product:

SUniProtKB:P42519

rasp EGFR ligand production

egfr_ligand_production_rasp

Participant: Gene Product: rasp

Gene Product:

raspUniProtKB:Q9VZU2

rho EGFR ligand production

egfr_ligand_production_rho

Participant: Gene Product: rho

Gene Product:

rhoUniProtKB:P20350

Function

serine-type endopeptidase activityGO:0004252

rho-4 EGFR ligand production

egfr_ligand_production_rho_4

Participant: Gene Product: rho-4

Gene Product:

rho-4UniProtKB:Q9VYW6

ru EGFR ligand production

egfr_ligand_production_ru

Participant: Gene Product: ru

Gene Product:

ruUniProtKB:Q9W0F8

Function

serine-type endopeptidase activityGO:0004252

stet EGFR ligand production

egfr_ligand_production_stet

Participant: Gene Product: stet

Gene Product:

stetUniProtKB:Q9W0E9

Function

serine-type endopeptidase activityGO:0004252

Part 2: secreted ligands

EGFR ligandsSignaling Pathwayegfr_ligands

Spitz, Keren and Gurken are TGF-alpha-like ligands; Vein is a secreted neuregulin-like ligand that is not processed by rhomboids.

growth factor activityGO:0008083

Part 3: receptor tyrosine kinase

EgfrSignaling Pathwayegfr_receptor

Annotons

Egfr Egfr

egfr_receptor_egfr

Participant: Gene Product: Egfr

Gene Product:

EgfrUniProtKB:P04412

Function

epidermal growth factor receptor activityGO:0005006

Part 4: phosphotyrosine adaptors, phosphatase and exchange factors

Receptor adaptors and Ras activationSignaling Pathwayegfr_adaptors_and_ras_activation

Drk and Shc bind the activated receptor; Corkscrew (SHP2) is a tyrosine phosphatase required for full Ras activation; Sos is the Ras exchange factor. Vav, a Rho-family exchange factor, is listed by FlyBase as both a core component and a negative regulator.

Annotons

drk Receptor adaptors and Ras activation

egfr_adaptors_and_ras_activation_drk

Participant: Gene Product: drk

Gene Product:

drkUniProtKB:Q08012

Shc Receptor adaptors and Ras activation

egfr_adaptors_and_ras_activation_shc

Participant: Gene Product: Shc

Gene Product:

ShcUniProtKB:Q9V3C8

csw Receptor adaptors and Ras activation

egfr_adaptors_and_ras_activation_csw

Participant: Gene Product: csw

Gene Product:

cswUniProtKB:P29349

Function

protein tyrosine phosphatase activityGO:0004725

Sos Receptor adaptors and Ras activation

egfr_adaptors_and_ras_activation_sos

Participant: Gene Product: Sos

Gene Product:

SosUniProtKB:P26675

Function

guanyl-nucleotide exchange factor activityGO:0005085

Vav Receptor adaptors and Ras activation

egfr_adaptors_and_ras_activation_vav

Participant: Gene Product: Vav

Gene Product:

VavUniProtKB:Q9NHV9

Part 5: small GTPase switch

Ras85DSignaling Pathwayegfr_ras

Annotons

Ras85D Ras85D

egfr_ras_ras85d

Participant: Gene Product: Ras85D

Gene Product:

Ras85DUniProtKB:P08646

Function

GTPase activityGO:0003924

Part 6: kinase cascade and scaffolds

Raf-Dsor1-Rolled MAP kinase cascadeSignaling Pathwayegfr_mapk_cascade

Raf (MAPKKK) phosphorylates Dsor1 (MEK), which phosphorylates Rolled (ERK). KSR, CNK and Aveugle are scaffolds that promote Raf activation.

MAP kinase activityGO:0004707

ksr Raf-Dsor1-Rolled MAP kinase cascade

egfr_mapk_cascade_ksr

Participant: Gene Product: ksr

Gene Product:

ksrUniProtKB:Q24171

cnk Raf-Dsor1-Rolled MAP kinase cascade

egfr_mapk_cascade_cnk

Participant: Gene Product: cnk

Gene Product:

cnkUniProtKB:A1ZAS2

ave Raf-Dsor1-Rolled MAP kinase cascade

egfr_mapk_cascade_ave

Participant: Gene Product: ave

Gene Product:

aveUniProtKB:Q8ML92

Part 7: transcription factors and co-repressor turnover

Nuclear transcriptional outputSignaling Pathwayegfr_nuclear_output

Pointed is the ETS activator of target genes; Yan (Aop), Capicua (with the co-repressor Groucho) and Tramtrack are repressors that are relieved downstream of ERK. Phyllopod and Ebi act in signal-dependent turnover of repressors. Zpr1 is a FlyBase core component with less defined role.

DNA-binding transcription repressor activity, RNA polymerase II-specificGO:0001227

phyl Nuclear transcriptional output

egfr_nuclear_output_phyl

Participant: Gene Product: phyl

Gene Product:

phylUniProtKB:Q27934

ebi Nuclear transcriptional output

egfr_nuclear_output_ebi

Participant: Gene Product: ebi

Gene Product:

ebiUniProtKB:Q95RJ9

Zpr1 Nuclear transcriptional output

egfr_nuclear_output_zpr1

Participant: Gene Product: Zpr1

Gene Product:

Zpr1UniProtKB:Q9W379