Insulin Receptor
Introduction
Insulin receptor (IR) is a transmembrane receptor, an important member to a large family of tyrosine kinase receptor proteins. Endogenous ligands such as insulin, IGF-1 (Insulin-like growth factor-1) and IGF-2 (Insulin-like growth factor-2) bind to this receptor to carry out major physiological and metabolic functions. INSR (Insulin Receptor) gene encodes a preproprotein that is proteolytically processed in our body to form a functional heterotetrameric insulin receptor. In mammals INSR gene can contain an additional exon 11 which may get encoded to form the IR isoform B or may be skipped in a tissue-specific manner forming the IR isoform A. This contributes to the major functional difference between the two isoforms, such that isoform A has more affinity for IGF-2. (1)
Occurrence
Insulin receptor occurs in the plasma membrane of a variety of cells in brain (olfactory bulb, hypothalamus, cerebral cortex, cerebellum, hippocampus, neurons, and pituitary lobe), kidney, liver (heapatocytes), heart, lungs (pulmonary alveoli), …show more content…
The β subunit are three domains, namely extracellular, transmembrane and cytosolic. (4) The IR contains an ATP-binding site in the cytosolic cluster of three tyrosine kinase residues (tyrosine kinase domain) which gets activated on insulin-binding through the kinase activation loop. These are connected to the 2β subunits, one at each intracellular part of IR. When insulin is not bound to the receptor, these are held in constrained form, but on binding of insulin at the ligand binding site on 2α subunits, constraints are freed, tyrosine kinase phosphorylate and activate each other, and then they phosphorylate other proteins in the signal transduction pathway.
Introduction
Insulin receptor (IR) is a transmembrane receptor, an important member to a large family of tyrosine kinase receptor proteins. Endogenous ligands such as insulin, IGF-1 (Insulin-like growth factor-1) and IGF-2 (Insulin-like growth factor-2) bind to this receptor to carry out major physiological and metabolic functions. INSR (Insulin Receptor) gene encodes a preproprotein that is proteolytically processed in our body to form a functional heterotetrameric insulin receptor. In mammals INSR gene can contain an additional exon 11 which may get encoded to form the IR isoform B or may be skipped in a tissue-specific manner forming the IR isoform A. This contributes to the major functional difference between the two isoforms, such that isoform A has more affinity for IGF-2. (1)
Occurrence
Insulin receptor occurs in the plasma membrane of a variety of cells in brain (olfactory bulb, hypothalamus, cerebral cortex, cerebellum, hippocampus, neurons, and pituitary lobe), kidney, liver (heapatocytes), heart, lungs (pulmonary alveoli), …show more content…
The β subunit are three domains, namely extracellular, transmembrane and cytosolic. (4) The IR contains an ATP-binding site in the cytosolic cluster of three tyrosine kinase residues (tyrosine kinase domain) which gets activated on insulin-binding through the kinase activation loop. These are connected to the 2β subunits, one at each intracellular part of IR. When insulin is not bound to the receptor, these are held in constrained form, but on binding of insulin at the ligand binding site on 2α subunits, constraints are freed, tyrosine kinase phosphorylate and activate each other, and then they phosphorylate other proteins in the signal transduction pathway.