Drosophila insulin-like peptides (Ilps), several of them secreted by the insulin-producing cells of the brain, bind the single insulin-like receptor InR, a receptor tyrosine kinase. Activated InR phosphorylates the adaptor Chico (IRS) and acts with the adaptor Lnk (SH2B), recruiting the class IA phosphatidylinositol 3-kinase made of the catalytic subunit Pi3K92E (Dp110) and the regulatory subunit Pi3K21B (p60). The resulting PIP3 recruits Pdk1 and Akt; Akt phosphorylates and excludes the transcription factor FOXO from the nucleus and promotes TORC1 activity through Rheb, leading to S6 kinase activation and inhibition of the translational repressor Thor (4E-BP). The pathway controls cell and organismal growth, carbohydrate and lipid metabolism, reproduction and lifespan.
Boundary. Core components (FlyBase INS-C) and the class IA PI3K complex (PI3K-IA). Ilp1, Ilp4, Ilp7 and Ilp8 are not FlyBase core members and are not included. The TORC1 and MAPK branches are shared with TOR and Ras signaling modules. Pten, Tsc1/gigas, ImpL2 and other FlyBase regulators are not parts. The other-effectors part collects FlyBase core members whose position in the pathway is tissue-specific; no activities are asserted for them. FlyBase groups realized by this module: PI3K-IA (FBgg0000903), INS (FBgg0000910). Subgroups folded into it: INS-C. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: INS-P (positive regulators of insulin-like receptor signaling pathway, 22 genes); INS-N (negative regulators of insulin-like receptor signaling pathway, 29 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_insulin_like_receptor_signaling.yaml. Member genes with a gene review in this repository: Akt, drk, Dsor1, mTor, Pdk1, raptor, rl, sima, tgo.
All recommended fields populated.
✗ none found
No MODULE:dmel_insulin_like_receptor_signaling deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
6 gene-function check(s) reflected in core functions · 0 conflict(s) · 9 evidence or coverage gap(s) (15 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 |
|---|---|---|---|
| insulin_like_peptides_ilp2 | Ilp2 UniProtKB:Q9VT51 Gene |
hormone activity GO:0005179 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| insulin_like_peptides_ilp3 | Ilp3 UniProtKB:Q9VT52 Gene |
hormone activity GO:0005179 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| insulin_like_peptides_ilp5 | Ilp5 UniProtKB:Q7KUD5 Gene |
hormone activity GO:0005179 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| insulin_like_peptides_ilp6 | Ilp6 UniProtKB:Q9W4Z4 Gene |
hormone activity GO:0005179 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| insulin_like_receptor_inr | InR UniProtKB:P09208 Gene |
insulin receptor activity GO:0005009 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| class_ia_pi3k_complex/pi3k92e | Pi3K92E UniProtKB:A0A0B4KGE8 Complex Unit |
1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| pdk1_akt_pdk1 | Pdk1 UniProtKB:Q9W0V1 Gene |
3-phosphoinositide-dependent protein kinase activity GO:0004676 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| pdk1_akt_akt | Akt UniProtKB:Q8INB9 Gene |
protein serine/threonine kinase activity GO:0004674 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| foxo_output_foxo | foxo UniProtKB:Q95V55 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. |
| foxo_output_fkh | fkh UniProtKB:P14734 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. |
| torc1_branch_rheb | Rheb UniProtKB:Q9VND8 Gene |
GTPase activity GO:0003924 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| torc1_branch_mtor | mTor UniProtKB:Q9VK45 Gene |
protein serine/threonine kinase activity GO:0004674 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| torc1_branch_s6k | S6k UniProtKB:Q94533 Gene |
ribosomal protein S6 kinase activity GO:0004711 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| inr_mapk_branch_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). |
| inr_mapk_branch_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). |
✓ every negative regulator described as feedback has an upstream edge closing the loop.
3 complete review(s) · 10 with deep research · 19 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| Pi3K92E A0A0B4KGE8 | ✗ | — | — |
| Lnk A0A0B4LHY5 | ✗ | — | — |
| cnk A1ZAS2 | ✗ | — | — |
| Sik3 A1ZBC4 | ✗ | — | — |
| Akt1 Q8INB9 | ✓ | 94/104 | ✓ |
| drk Q08012 | ✓ | 74/76 | ✓ |
| Dsor1 Q24324 | ✓ | ✓ | ✓ |
| HDAC4 M9PHQ2 | ✗ | — | — |
| mTor Q9VK45 | ✓ | 76/77 | ✓ |
| InR P09208 | ✗ | — | — |
| fkh P14734 | ✗ | — | — |
| Pdk1 Q9W0V1 | ✓ | 47/49 | ✓ |
| Pi3K21B Q7KTZ2 | ✗ | — | — |
| Ilp5 Q7KUD5 | ✗ | — | — |
| S6k Q94533 | ✗ | — | — |
| foxo Q95V55 | ✗ | — | — |
| Ilp2 Q9VT51 | ✗ | — | — |
| Ilp3 Q9VT52 | ✗ | — | — |
| Myc Q9W4S7 | ✗ | — | — |
| Ilp6 Q9W4Z4 | ✗ | — | — |
| Sik2 Q9W532 | ✗ | — | — |
| Glyp Q9XTL9 | ✗ | — | — |
| chico Q9XTN2 | ✗ | — | — |
| Thor Q9XZ56 | ✗ | — | — |
| raptor Q9W437 | ✓ | 21/23 | ✓ |
| Rheb Q9VND8 | ✓ | ✓ | ✓ |
| rl P40417 | ✓ | 119/125 | ✓ |
| sima Q24167 | ✓ | ✓ | ✓ |
| tgo O15945 | ✓ | 56/57 | ✓ |
Insulin-like peptides activate InR, Chico/Lnk and class IA PI3K, then Pdk1-Akt, which inhibits FOXO and activates TORC1-S6K growth signaling.
Chico (IRS) and Lnk (SH2B) are InR adaptors; Drk (Grb2) links InR to Ras-MAPK.
Pi3K92E (Dp110) catalytic and Pi3K21B (p60) regulatory subunits.
FOXO is the main transcriptional effector repressed by Akt. Fork head is a FlyBase core component acting in some tissues.
Rheb activates TORC1 (mTor with Raptor), which phosphorylates S6 kinase and the 4E-BP Thor.
FlyBase core components acting downstream of InR in particular tissues or physiological contexts: the salt-inducible kinases Sik2 and Sik3, HDAC4, Myc, the hypoxia factor Sima with its partner Tango, and glycogen phosphorylase (Glyp).