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UVM BCOR 103 - Exam 3 Study Guide
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BCOR 103 1st EditionExam # 3 Study Guide Lectures: 15-20Lecture 15 (March 17)Cell Signaling in Nature:-detect nutrients-detect energy/light sources-monitor environment-cell-cell communication-coordinate cellular eventsCellular Responses to Signals:-movement-embryogenesis-programmed cell death-metabolism-cell differentiationOverview of Eukaryotic Cell Signaling- Cell signaling: converting environmental input signals to output cellular responses.- Input signals: light, sound, smell, small molecules, nutrients, cell-cell interactions.- Output cellular responses: cell division, differentiation/development, cell structural changes, motility, metabolism, survival/cell death.- Signal transduction: transmitting input signal into cell to induce complex cellular responses through changes in gene expression or protein function. Methods for Studying Signaling Pathways-methods that examine cellular processes in response to specific signals or signaling pathways.1. Measure levels of protein expression: immunoblot analysis (Western Blot) using antibodies todetect proteins. 2. Examine protein-protein interactions: co-immunoprecipitation; GST pull downs; two hybrid analysis.3. Enzymatic Assays: establish enzyme activity. 4. Microscopy: visualize protein localization, cell structure, and DNA content.Protein Kinase Mechanisms:-Protein Kinase and phosphatases modify functions of enzymes in response to signals.-Kinase puts phosphate groups on serine, threonine, or tyrosine amino acids (phosphorylates them).-Phosphatases take the phosphate groups off. Genetic Methods for Studying Signaling Pathways:-mutations: activate or block pathways independent of signal-used to determine relationships between signaling compounds. Types of Cell Signaling:-Direct Cell to Cell Signaling-Signaling by Secreted MoleculesA. Endocrine SignalingB. Paracrine SignalingC. Autocrine SignalingOvercoming Intracellular Obstacles to Proper Signaling- Major obstacles:o Passing signals through membranes and cytoplasmo Relative size of signaling molecule compared to the cello Coordination of events: right time, right place- Overcoming obstacles in signaling:o Proper localization of signaling factors (into membranes)o Protein-protein interactions (multi-protein complexes)o Turn signals ON/OFF by: Molecular switches Phosphorylation Proteolysiso Signaling networksSimplified Classification of Signaling ComponentsSignaling Molecules receptors transmitters ultimate target Gene Expression OR Protein FunctionSignaling Molecules: the signal initiators- Signals bind cell-surface receptors expressed on plasma membranes of target cells or diffuse through plasma membrane to bind intracellular receptors.- Binding induces conformational and/or enzymatic changes in receptors to initiate intracellular signaling.- Vary in structure:o Gases, peptides, lipids, etc.o Structure determines type of signaling- Vary in function:o Varying distances, modes of action- Endocrine signals:o Hormones secreted by endocrine cellso Carried through bloodstreamo Act on target cells at distant body sites- Endocrine signaling molecules:o Hydrophobic steroid hormoneso Related hydrophobic signaling molecules- Target cells have receptors for binding specific hormoneso “pull” appropriate hormones from extracellular fluid- Sex hormones*o Made by gonadso Required for development and maintenance of reproductive system- Glucocorticoids: (cortisol)*o Stimulates production of glucose- Mineralocorticoids: (aldosterone)*o Regulate salt and water balance in kidneys*all synthesized from cholesterol*- Thyroid hormoneo Role in developmento Regulates metabolism- Vitamin Do Regulates Ca++ functions- Retinoic Acido Synthesized from Vitamin Ao Role in vertebrate developmentHormone Receptors act as Transcription FactorsCommon Domains of steroid receptor superfamily:-hormone binding-DNA binding-transcriptional regulation-nuclear targetingSteroid Hormone Binding activates Receptor Dimerization- Steroid hormone signaling begins with the hydrophobic steroid diffusing through the plasma and nuclear membranes. Hormone binds steroid receptor in nucleus (the receptor alone can’t bind to DNA and is inactive).- Upon binding, receptor undergoes conformational change leading to displacement of Hsp90 and dimerization.- Steroid hormone/receptor protein complex binds to DNA to regulate transcription, which leads to a cellular response. An Example: HAT: histone acetyltransferase-modifies histones, thereby de-condensing chromatin-activates transcriptionThyroid Hormones Activate DNA-bound receptor- Thyroid hormone signaling begins with the thyroid hormone diffusing through the plasma and nuclear membranes. - The thyroid hormone binds to the thyroid hormone receptor in nucleus (already bound to DNA but inactive).- Upon hormone binding, receptor undergoes conformational change. - Thyroid hormone/receptor complex regulates transcriptionAn Example: HDAC: histone deacetylase-inhibits chromatin de-condensation-inhibits transcriptionOverview of Paracrine Signaling- Paracrine signaling molecules:o Are secreted by a variety of cellso Act locally on target cells- Types of paracrine signaling molecules:o Gases (diffuse across membrane), have a short half-lifeo Neurotransmitterso Peptide hormones and growth factorso Eicosanoids- Types of paracrine receptorso Cell surface receptorso Common domains: Extracellular ligand binding domain Membrane-spanning domain Cytosolic catalytic domainParacrine Signaling by Gases: Nitric Oxide (NO)- NO: made by deamination of arginine- Regulates many processes in many cells- Short half-life (5-10 seconds)- effects are rapidNO Relaxes Vascular Smooth Muscle Cells - NO relaxes vascular smooth muscle cells (VSMCs) in arteriole walls:o Endothelial cells that line blood vessels release a puff of Nitric Oxide that diffusesinto underlying VSMCs causing them to relax. o Leads to vasodilation and increased blood flow- Nitroglycerin is converted to NO:o Used for ~100 years to relax blood vessels in patients with angina. NO Target: Guanylyl Cyclase- Nitric Oxide stimulates Guanylyl cylase (sGC)- which makes more cGMP- cGMP activated multiple targets including cGMP dependent kinases and cGMP gated ionchannels- cGMP production is balanced by degradation to 5’ GMP by phosphodiesterase (PDE)- Viagra and Cialis inhibit PDE which blocks cGMP conversion to 5’GMP and leads to sustained blood flow in VSMCs. Paracrine Signaling: Neurotransmitters*- Neurotransmitter


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