bis104 benjamin edward quiz and exams and notes_0002 - Page 4

Bis104 benjamin edward quiz and exams and notes_0002 - Page 4

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Insulin; signaling by a Receptor Tyrosinc Kinase (RTK) 1. Other ligands with similar mechanism: growth hormone, epidermal growth factor, plate-derived growth factor, fibroblast factor, VEGF. 2. General features (figure 15.15) a. RTKs are a signaling superfamily; about 50 genes have been identified. b. They are single pass integral membrane proteins with inner (kinase activity) and outer (binding site for ligand) domains, 3. Insulin receptor (figure 15.22) Tetramer: 2 alpha units + 2 beta units. Alpha = ligand (insulin) binding site. Beta = membrane spanning protein with kinase activity. 4. Signaling sequence (figure 15.23) a. insulin production (Islets of Langerhans; beta cells of pancreas) b. Insulin binds to receptors on target cells (adipocytcs, muscle cells) c. Target cells respond:
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Unformatted text preview: dimerization of receptors; auto-phosphorylation phosphorylation of insulin receptor substrates (IRSs) increase GLUT-4 receptor on PM glucose uptake; polymerization (glycogen synthesis) lipid and protein synthesis cell proliferation d. Phosphorylatcd IRSs provide docking and activation stations for proteins with SH2 (src homology- 2) domains (high affinity for phospho-tyrosines) Example: P13K binds to IRS P13K phosphorylatcs PIP to make PIP2 and PIP3 PIP2 localizes at PM inner leaflet Bound PIP2 recruits protein kinase B (PKB) to membrane PDK1 phosphorylatcs PKB PKB stimulates protein synthesis; glucose uptake, glycogen synthesis A divergent signaling pathway. A single ligand (insulin) stimulates multiple cascade pathways. Demo...
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This note was uploaded on 05/24/2010 for the course BIS 104 taught by Professor Scholey during the Spring '08 term at UC Davis.

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