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

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1Skeletal muscle cellEIF2B2MURF1SMAD2PDK1N-WASPActRIIBNFKB1GSK3Bamino acidsJNKIgfbp54EPBAMPKPTENActin polymerization& MyofibrillogenesisIGF1recTNFrecILKProtein synthesisSMAD3TWEAKPI3KTNFrecFoxO TNFaNEBMyostatinAMPKPGC1MAFbxIntegrin B1S6KmTORC2IGF1MTORAKT1mTORC1LC3IRS1PLD1TNFaProtein degradationProtein synthesis


Description

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. This pathway is based on figure 1 from Schiaffino et al.

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Bibliography

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

History

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CompareRevisionActionTimeUserComment
90178view17:23, 21 October 2016KhanspersModified description
90125view05:13, 14 October 2016Khansperssimplified
89264view18:09, 27 August 2016KhanspersReverted to version '20:05, 14 August 2016' by Khanspers
89263view18:07, 27 August 2016Khansperschanged SMAD2/3 from complex to group
88788view20:05, 14 August 2016AAR&CoEdited Data Node
88778view19:48, 14 August 2016AAR&CoModify Datanode
88776view19:45, 14 August 2016AAR&CoModify Datanode
88773view19:41, 14 August 2016AAR&CoModify Datanodes
88707view17:02, 12 August 2016AAR&CoAdded Data Node
88706view17:01, 12 August 2016AAR&CoUpdated Data Nodes
88705view16:54, 12 August 2016AAR&CoPeriodical save, work in progress
88704view16:44, 12 August 2016AAR&CoPeriodical save, work in progress
88698view16:06, 12 August 2016AAR&CoPeriodical save, work in progress
88691view15:55, 12 August 2016AAR&CoPeriodical save, work in progress
88681view15:45, 12 August 2016AAR&CoPeriodical save, work in progress
88677view15:42, 12 August 2016AAR&CoPeriodical Save
88671view15:35, 12 August 2016AAR&CoPeriodical save, work in progress
88664view15:24, 12 August 2016AAR&CoAdded Pathway Nodes
88660view15:15, 12 August 2016AAR&CoModified description
88164view08:31, 29 July 2016Mkutmonunconnected line
87346view20:34, 21 July 2016AlexanderPicoChanged one gene over to mouse
87345view18:34, 21 July 2016AlexanderPicoReverted to version '16:35, 17 July 2016' by AlexanderPico
87192view08:34, 19 July 2016EgonwFixed the species.
87057view23:35, 17 July 2016AlexanderPicoOntology Term : 'insulin-like growth factor signaling pathway' added !
87056view23:34, 17 July 2016AlexanderPicoOntology Term : 'signaling pathway' added !
87055view23:34, 17 July 2016AlexanderPicoOntology Term : 'PW:0000004' removed !
87054view23:34, 17 July 2016AlexanderPicoOntology Term : 'growth factor signaling pathway' added !
87053view23:33, 17 July 2016AlexanderPicoOntology Term : 'cell of skeletal muscle' added !
87052view23:33, 17 July 2016AlexanderPicoOntology Term : 'regulatory pathway' added !
87051view23:31, 17 July 2016AlexanderPicoAdded lit ref
87050view23:30, 17 July 2016AlexanderPicoFixed interactions, pathway nodes, cell and layout
86130view13:06, 1 July 2016AAR&CoModified description
86129view13:06, 1 July 2016AAR&CoNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
4EPBGeneProductENSMUSG00000028156 (Ensembl) EIF4E
AKT1GeneProductENSMUSG00000001729 (Ensembl)
AMPKGeneProductENSG00000111725 (Ensembl)
ActRIIBGeneProductENSG00000114739 (Ensembl)
Actin polymerization & MyofibrillogenesisPathwayWP523 (WikiPathways)
EIF2B2GeneProductENSG00000119718 (Ensembl)
FoxO GeneProductfamily of transcription factors
GSK3BGeneProductENSG00000082701 (Ensembl)
IGF1GeneProductENSG00000017427 (Ensembl)
IGF1rec GeneProductENSG00000140443 (Ensembl)
ILKGeneProductENSG00000166333 (Ensembl)
IRS1GeneProductENSG00000169047 (Ensembl) not sure, because also 2, 3, 4
Igfbp5GeneProductENSMUSG00000026185 (Ensembl) most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
Integrin B1GeneProductENSG00000150093 (Ensembl)
JNKProteinA0A087WVY6 (Uniprot-TrEMBL)
LC3GeneProductENSG00000101460 (Ensembl)
MAFbxGeneProductENSG00000156804 (Ensembl) FBXO32/atrogin-1
MTORGeneProductENSG00000198793 (Ensembl)
  • effect of AKT on MTOR is indirect
  • Part of two multiprotein complexes, TORC 1 and TORC 2
MURF1 GeneProductENSG00000158022 (Ensembl) TRIM63
MyostatinGeneProductENSG00000138379 (Ensembl)
N-WASPGeneProductENSG00000106299 (Ensembl)
NEBGeneProductENSG00000183091 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
PDK1GeneProductENSG00000152256 (Ensembl)
PGC1 GeneProductENSG00000109819 (Ensembl)
PI3KGeneProductENSG00000105851 (Ensembl) phosphatidlinositol 3-kinase
PLD1GeneProductENSG00000075651 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
Protein degradation PathwayWP519 (WikiPathways)
Protein synthesisPathway
S6KGeneProductENSG00000108443 (Ensembl)
SMAD2GeneProductENSG00000175387 (Ensembl)
SMAD3GeneProductENSG00000166949 (Ensembl)
TNFaGeneProductENSG00000228978 (EcoGene)
TNFaGeneProductENSG00000228978 (Ensembl)
TNFrecGeneProductENSG00000067182 (Ensembl)
TWEAKGeneProductENSG00000125657 (Ensembl)
amino acids
mTORC1
  • Complex of mTOR when bound to Raptor
  • rapamycin sensitive
mTORC2
  • complex of mTOR when bound to rictor
  • rapamycin insensitive
  • maximizes activation of AKT1

Annotated Interactions

No annotated interactions

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