Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling (WP3850)

Homo sapiens

The signaling pathway that involves insulin-like growth factor 1 (IGF1), and a variety of other components that affect the pathway, plays an important role in the regulation of skeletal muscle growth. The kinase Akt, or protein kinase B (PKB), is a central component in the pathway and is involved in both muscle synthesis, through mammalian target of rapmycin (mTOR) and glycogen synthase kinase 3B (GSK3B), and muscle degradation, through the transcription factors of the FoxO family. The pathway also involves several feedback loops such as the negative feedback of S6K, phosphorylated by mTORC1, which inhibits IRS, or the positive feedback of mTORC2, which is necessary to maximize the activation of Akt. A variety of other factors and pathways also influence the IGF1-Akt signaling pathway at various points. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3850 CPTAC Assay Portal]


Alex Pico , Martina Summer-Kutmon , Kristina Hanspers , Friederike Ehrhart , and Eric Weitz


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Homo sapiens



Pathway Ontology

signaling pathway growth factor signaling pathway insulin-like growth factor signaling pathway

Cell Type Ontology

cell of skeletal muscle


Label Type Compact URI Comment
amino acids Metabolite chebi:33709
GSK3B GeneProduct ensembl:ENSG00000082701
PI3K GeneProduct ensembl:ENSG00000105851 phosphatidlinositol 3-kinase
SMAD3 GeneProduct ensembl:ENSG00000166949
4EPB GeneProduct ensembl:ENSG00000151247 EIF4E
EIF2B2 GeneProduct ensembl:ENSG00000119718
N-WASP GeneProduct ensembl:ENSG00000106299
PGC1 GeneProduct ensembl:ENSG00000109819
SMAD2 GeneProduct ensembl:ENSG00000175387
AMPK GeneProduct ensembl:ENSG00000111725
Myostatin GeneProduct ensembl:ENSG00000138379
MLST8 GeneProduct ensembl:ENSG00000167965
TWEAK GeneProduct ensembl:ENSG00000125657
AKT1 GeneProduct ensembl:ENSG00000142208
Integrin B1 GeneProduct ensembl:ENSG00000150093
NEB GeneProduct ensembl:ENSG00000183091
MAFbx GeneProduct ensembl:ENSG00000156804 FBXO32/atrogin-1
LC3 GeneProduct ensembl:ENSG00000101460
AKT1S1 GeneProduct ensembl:ENSG00000204673
TNFrec GeneProduct ensembl:ENSG00000067182
MURF1 GeneProduct ensembl:ENSG00000158022 TRIM63
IRS1 GeneProduct ensembl:ENSG00000169047 not sure, because also 2, 3, 4
PLD1 GeneProduct ensembl:ENSG00000075651
TNFrec GeneProduct ensembl:ENSG00000067182
ILK GeneProduct ensembl:ENSG00000166333
PDK1 GeneProduct ensembl:ENSG00000152256
MTOR GeneProduct ensembl:ENSG00000198793 effect of AKT on MTOR is indirect
Part of two multiprotein complexes, TORC 1 and TORC 2
S6K GeneProduct ensembl:ENSG00000108443
TNF GeneProduct ecogene:ENSG00000228978
AMPK GeneProduct ensembl:ENSG00000111725
PTEN GeneProduct ensembl:ENSG00000171862
IGF1rec GeneProduct ensembl:ENSG00000140443
TNF GeneProduct ensembl:ENSG00000228978
RPTOR GeneProduct ensembl:ENSG00000141564
IGF1 GeneProduct ensembl:ENSG00000017427
DEPTOR GeneProduct ensembl:ENSG00000155792
IGFBP5 GeneProduct ensembl:ENSG00000115461 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
ActRIIB GeneProduct ensembl:ENSG00000114739
NFKB1 GeneProduct ensembl:ENSG00000109320
MTOR GeneProduct ensembl:ENSG00000198793 effect of AKT on MTOR is indirect
Part of two multiprotein complexes, TORC 1 and TORC 2
MLST8 GeneProduct ensembl:ENSG00000167965
MAPKAP1 GeneProduct ensembl:ENSG00000119487
RICTOR GeneProduct ensembl:ENSG00000164327
MTOR GeneProduct ensembl:ENSG00000198793 effect of AKT on MTOR is indirect
Part of two multiprotein complexes, TORC 1 and TORC 2
JNK Protein uniprot:A0A087WVY6


  1. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Schiaffino S, Mammucari C. Skelet Muscle. 2011 Jan 24;1(1):4. PubMed Europe PMC Scholia