Sandbox Reserved 427: Difference between revisions
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The insulin receptor is a tyrosine kinase, that is a type of ligand-activated receptor kinase. Insulin receptors are expressed at the cell surface as disulfide-linked homodimers composed of alpha/beta <scene name='Sandbox_Reserved_427/Rcb_monomer_fabsfaded/1'>monomers</scene>. The folded over conformation of the ectodomain places ligands in the correct relative positions for activity. ('''green scene''') The receptor mediates activity by the addition of phosphate to tyrosines on specific proteins in cell | The insulin receptor is a tyrosine kinase, that is a type of ligand-activated receptor kinase. Insulin receptors are expressed at the cell surface as disulfide-linked homodimers composed of alpha/beta <scene name='Sandbox_Reserved_427/Rcb_monomer_fabsfaded/1'>monomers</scene>. The folded over conformation of the ectodomain places ligands in the correct relative positions for activity. ('''green scene''') The receptor mediates activity by the addition of phosphate to tyrosines on specific proteins in cell | ||
Insulin receptors are found in many diverse organisms organisms, from cnidarians and insects to humans. In humans, correctly functioning insulin receptors are essential for maintaining glucose levels in the blood. The insulin receptor also has role in growth and development (through insulin growth factor II); studies have shown that signalling through IGF2 plays a role in the mediation embryonic growth | Insulin receptors are found in many diverse organisms organisms, from cnidarians and insects to humans. In humans, correctly functioning insulin receptors are essential for maintaining glucose levels in the blood. The insulin receptor also has role in growth and development (through insulin growth factor II); studies have shown that signalling through IGF2 plays a role in the mediation embryonic growth. <ref>PMID: 12471165</ref> | ||
In everyday function, insulin receptor substrate 1 (IRS-1) binding leads to increase in the high-affinity glucose transporter (Glut4) molecules on the outer membrane of the cell in muscle and adipose tissue. Glut4 mediates the transport of glucose into the cell, so an increase in Glut4 leads to increased glucose uptake. Insulin has two different receptor-binding surfaces on opposite sides of the molecule, that interact with two different <scene name='Sandbox_Reserved_427/ | In everyday function, insulin receptor substrate 1 (IRS-1) binding leads to increase in the high-affinity glucose transporter (Glut4) molecules on the outer membrane of the cell in muscle and adipose tissue. Glut4 mediates the transport of glucose into the cell, so an increase in Glut4 leads to increased glucose uptake. Insulin has two different receptor-binding surfaces on opposite sides of the molecule, that interact with two different <scene name='Sandbox_Reserved_427/Rcb_dimer_bindinghighlighted/1'>sites on the insulin receptor</scene>sites on the insulin receptor. The first binding insulin surface interacts with a site on the <span style="color:blue">'''L1'''</span> module as well as a 12-amino-acid peptide from the insert in <span style="color:red">'''Fn2'''</span>. The second binding site consists of resides on the C-terminal portion of <span style="color:aqua">'''L2'''</span> and in the <span style="color:fuchsia">'''Fn1'''</span> and <span style="color:red">'''Fn2'''</span> modules <ref>PMID: 2657531</ref>. Binding sites are shown <scene name='Sandbox_Reserved_427/Rcb_dimer_bindinghighlighted2/1'>here</scene> highlighted in both monomers of the biologically fuctional dimer. <ref>PMID: 18991400</ref> | ||
Maintaining appropriate blood glucose levels is essential for appropriate life-sustaining metabolic function, and insulin receptor malfunction is associated with several severe diseases. Insulin insensitivity, or decreased insulin receptor signalling, leads to diabetes mellitus type 2. Type 2 diabetes is also known as non-insulin-dependent or adult onset diabetes, and is believed to be caused by a combination of obesity and genetic predisposition. In type 2 diabetes, cells are unable to uptake glucose due to decreased insulin receptor signaling, which leads to hyperglycemia (increased circulating glucose). Type 2 diabetes can be managed with dietary and lifestyle modifications to aid in proper metabolism. | Maintaining appropriate blood glucose levels is essential for appropriate life-sustaining metabolic function, and insulin receptor malfunction is associated with several severe diseases. Insulin insensitivity, or decreased insulin receptor signalling, leads to diabetes mellitus type 2. Type 2 diabetes is also known as non-insulin-dependent or adult onset diabetes, and is believed to be caused by a combination of obesity and genetic predisposition. In type 2 diabetes, cells are unable to uptake glucose due to decreased insulin receptor signaling, which leads to hyperglycemia (increased circulating glucose). Type 2 diabetes can be managed with dietary and lifestyle modifications to aid in proper metabolism. | ||
Mutations in both copies of the insulin receptor gene causes Donohue syndrome, which is also known as leprechaunism. Donohue syndrome is an autosomal recessive disorder that results in a totally non-functional insulin receptor. The disorder results in distorted facial features, severe growth retardation, and often death within a year. | Mutations in both copies of the insulin receptor gene causes Donohue syndrome, which is also known as leprechaunism. Donohue syndrome is an autosomal recessive disorder that results in a totally non-functional insulin receptor. The disorder results in distorted facial features, severe growth retardation, and often death within a year.<ref>PMID: 12023989</ref> A less severe mutation of the same gene causes a much milder form of the disease in which there is some insulin resistance but normal growth and subcutaneous fat distribution.<ref>PMID: 8326490</ref> | ||
===Overall Structure=== | ===Overall Structure=== | ||
