General Information:

Id: 964 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mammalia
review
Reference: Frojdo S et al.(2009) Alterations of insulin signaling in type 2 diabetes: a review of the current evidence from humans Biochim. Biophys. Acta 2: 83-92 [PMID: 19041393]

Interaction Information:

Comment Tyrosine phosphorylated IRS1/2 recruit the heterodimeric p85/p110 PI3K at the plasma membrane, where it produces the lipid second messenger PIP3, which in turn activates a serine/threonine phosphorylation cascade of PH-domain containing proteins.
Formal Description
Interaction-ID: 5941

protein modification

IRS1-phosTyr

increases_activity of

complex/PPI

Phosphatidylinositol 3-kinase

Comment Mechanistically, PDK1, PKB and atypical PKCs zeta and lambda, which all contain a PH-domain, are recruited at the plasma membrane by binding to PIP3; thereon, PDK1 phosphorylates PKB and atypical PKCs zeta and lambda on a threonine residue located in the activation loop of the catalytic domain, causing their activation.
Formal Description
Interaction-ID: 5950

gene/protein

PDPK1

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for PDPK1 or AKT1
Comment Upon PKB-mediated phosphorylation on Ser9, GSK-3 is inactivated.
Formal Description
Interaction-ID: 5956

gene/protein

AKT1

increases_phosphorylation of

gene/protein

GSK3B

at Ser9 of GSK3
Drugbank entries Show/Hide entries for AKT1 or GSK3B
Comment Activated IRS1/2 recruit Grb2, which associates to SOS and activates the Erk1/2 MAPK pathway.
Formal Description
Interaction-ID: 6038

gene/protein

IRS1

increases_quantity of

complex/PPI

GRB2-SOS complex

Drugbank entries Show/Hide entries for IRS1
Comment The action of insulin is initiated by binding to its cognate receptor and activation of the receptor's intrinsic protein tyrosine kinase activity, resulting in the phosphorylation of tyrosine residues located in the cytoplasmic face.
Formal Description
Interaction-ID: 73819

complex/PPI

Insulin receptor

increases_activity of