Reactome: A Curated Pathway Database
Attention
The EBI data centre will be shutting down from the afternoon (BST) of Friday 26th August until the afternoon of Tuesday 30th August 2016 for essential maintenance. This might have an impact on some Reactome services and we apologize for any inconvenience.

Internalisation of the insulin receptor

Stable Identifier
R-HSA-74718
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Almost concomitantly a second effect resulting from the tyrosine phosphorylation of the insulin receptor begins to occur. The phosphorylation of the tyrosine in the NPEY sequence found in the juxtamembrane is also a signal for endocytosis to occur. Whilst invagination of the plasma membrane commences the receptor tyrosine kinase activity continues unabated as does substrate phosphorylation.

As the invagination continues certain proteins are concentrated in the area of invagination. In addition to the insulin receptor itself there is a recruitment of insulin-specific protein tyrosine phosphatases (PTPs). This process takes less than one minute. (The identity of these PTPs is not clearly established yet. A discussion of candidates will be added in the near future.)

The formation of the endosome containing the activated ligand-receptor complex is completed within two minutes following ligand presentation at the plasma membrane and is maximal by five minutes. Endocytosis of activated receptors has the dual effect of concentrating receptors within endosomes and allowing the insulin receptor tyrosine kinase to phosphorylate substrates that are spatially distinct from those accessible at the plasma membrane. The endosome also contains other proteins crucial to the signal transduction process. These include a proton pump and the insulin degrading activity. It is not certain how these proteins arrive in the endosome since it could be via the endosome maturation or fusion pathways.

Literature References
PubMed ID Title Journal Year
Participants
Participant Of
Orthologous Events