Physiology Week 8 Lecture 14
Physiology Week 8 Lecture 14 IPHY 3470
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This 3 page Class Notes was uploaded by Sydney Lazzell on Wednesday October 12, 2016. The Class Notes belongs to IPHY 3470 at University of Colorado at Boulder taught by Christopher DeSouza in Fall 2016. Since its upload, it has received 21 views. For similar materials see Human Physiology 1 in integrated physiology at University of Colorado at Boulder.
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Date Created: 10/12/16
IPHY 3470: Human Physiology 1 Week 8 Lecture 14 Signal Pathway • Extracellular molecules activate signaling pathways to effect different cellular responses • Receptor locations (based on what ligand can do) o In cytosol vs. nucleus – lipidphilic = diffuses through cell membrane o Lipidphobic = on cell membrane (cell surface) • Membrane receptors (4 categories) 1. Receptor channel 2. Receptor enzyme 3. G protein-coupled receptor 4. Integrin receptor • Signal transduction o Receptor ligand complex activates an amplifier enzyme (AE) o Amplifier enzymes: § Adenylyl cyclase § Guanylyl cyclase § Phospholipase C Receptor Enzyme • Ex: Tyrosine kinase (insulin binds to TK) • Signal molecule binds to receptor –--> TK on cytoplasmic side –--> phosphorylated protein • Activation of one kinase can phosphorylate many enzymes (important for amplification) • 2 regions: receptor region (outside the cell) & enzyme region (cytoplasmic side) o Can be linked together but can also be separate • Ligand binding activates enzymes • Receptor enzymes either protein kinases (TK or GC converts GTP to cGMP; cGMP = second messenger) • Ligands bind receptor enzymes = insulin, growth factors, cytokines G Protein-Coupled Receptor • Membrane spanning • G protein = alpha, beta, gamma subunits • Stimulated by activated receptor, alpha subunit exchanges bound GDP for GTP • GTP bound alpha subunit dissociates from beta/gamma subunits & binds to nearby enzyme – alternating activity • GTP hydrolyzed to GDP (loose phosphate group) • 100’s of G proteins • Ligands bind to GPCR’s: hormones, growth factors, neurotransmitters • When activated: o Open an ion channel in the membrane o Alter enzyme activity in the cytoplasm • Linked to amplifier enzymes (2 most common): o Adenylyl cyclase (in plasma membrane) o Phospholipase C • cAMP = important second messenger (always linked w/adenylyl cyclase) o ---> protein kinase A ---> phosphorylation ---> cell response • AC amp enzyme – converts ATP to cAMP ---> PK-A ---> phosphorylation ---> cell response • Many lipidphilic hormones use GPCR-cAMP pathway Phospholipase C • Amplifying enzyme = PL-C • 2 second messengers: o DAG (plasma membrane) ---> protein kinase C ---> phosphorylation ---> cell response o IP3 (cytosol) ---> triggers release of Ca2+ (from ER) ---> cell response Calcium to Signal Transduction • Can enter through gated channels or be released from ER via second messenger • Bind w/calmodulin to exert a variety of effects (stabilize) • Versatile ionic messenger • Binds to proteins regulation exocytosis – GLUT 4 = increase of Ca2+ = muscle contraction
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