insulin receptor; IR; (INSR)

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Function

activated by insulin, IGF1 & IGF2
has a tyrosine-protein kinase activity
mediates the metabolic functions of insulin
- recruitment of GLUT-4 to the plasma membrane in adipocytes & skeletal muscle
binding to insulin stimulates association of the receptor with downstream mediators including IRS1 & phosphatidylinositol 3'-kinase (PI3K)
can activate PI3K either directly by binding to the p85 regulatory subunit, or indirectly via IRS1
isoform short has a higher affinity for insulin
interacts with SORBS1 but dissociates from it following insulin stimulation
binds SH2B2
interacts with the PID domains of IRS1 & SHC1 in vitro when autophosphorylated on Tyr
interacts with SH2 domains of 85 kD regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on Tyr
interacts with SOCS7
autophosphorylation activates the kinase activity
autophosphorylated on Tyr in response to insulin
phosphorylation of Tyr-999 is required for IRS1- & SHC1- binding

derived from single-chain precursor preproinsulin receptor
tetramer of 2 alpha & 2 beta chains linked by disulfide bonds
the alpha chains contribute to the formation of the ligand-binding domain
the beta chains carry the kinase domain
after being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated & then cleaved, followed by its transport to the plasma membrane
belongs to the protein kinase superfamily, Tyr protein kinase family, insulin receptor subfamily
contains 2 fibronectin F3 modules
contains 1 protein kinase domain
sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition

membrane

isoform long & isoform short are expressed in the peripheral nerve, kidney, liver, striated muscle, fibroblasts & skin
isoform short is expressed also in the spleen & lymphoblasts