Reactome | Internalisation of the insulin receptor

Internalisation of the insulin receptor

Stable Identifier

R-HSA-74718

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

endosome membrane, plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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.)

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
9609114	Insulin receptor internalization and signalling. Baass, PC, Drake, PG, Bergeron, JJ, Authier, F, Posner, BI	Mol Cell Biochem	1999
8760075	Compartmentalization of protein traffic in insulin-sensitive cells. Pilch, PF, Kandror, KV	Am J Physiol	1996
18406720	Intracellular Signal Transduction: The Role of Endosomes Bevan, AP, Drake, PG, Bergeron, JJ, Posner, BI	Trends in Endocrinology and Metabolism	1996