biosignaling - creightonchemistry.creighton.edu/~jksoukup/lec13stud.pdf · biosignaling cells -...
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BiosignalingCells - receive and act on signalsSignal brings about response
Types of signals:Autocrine -Paracrine -Endocrine -
Lots of signals but just a few evolutionarily conserved mechanismsto detect signals and transduce them into change in cell
Weak interactionsReceptor cell-specificHigh affinity of receptors for signalCooperativity
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BiosignalingTypes of signal transducers
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BiosignalingI. Ligand-gated Ion Channel
Nicotinic Acetylcholine receptoropens in response to neurotransmitter acetylcholine and to nicotineFound in neurons and muscle fibers
Receptor = Allosteric proteinCooperative binding of Ach
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BiosignalingII. Receptor Enzymes
Insulin ReceptorLigand-binding domain on extracellular surface of plasma membraneEnzyme active site on cytosolic side
nucleus
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BiosignalingII. Receptor EnzymesInsulin Receptor
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BiosignalingIII. G protein-coupled Receptors and Second Messengersβ-Adrenergic Receptor
a.k.a. AdrenalineRegulates metabolism in muscle, liver and fatBreakdown of glycogen and fat
Serpentine receptor - 7 transmembrane helices
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BiosignalingIII. G protein-coupled Receptors and Second MessengersEpinephrine
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BiosignalingIV. Steroid receptorsAct in nucleus to alter gene expressionSteroid hormones (estrogen, progesterone, cortisol, etc.) hydrophobicReceptors (proteins) and HREs (hormone response elements inDNA)
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BiosignalingIV. Steroid receptorsReceptor for estrogenBreast cancer - some types need estrogen present for tumor growthTamoxifen = antagonist of estrogenTamoxifen competes with estrogen for binding to receptorTamoxifen has no effect on gene expression like estrogen does
RU486 = antagonist of progesteroneCompetes with prog for binding to receptorProg needed for proper implantation of fertilized ovum in uterus
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BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Tumors --> result of uncontrolled cell division - biosignaling goneBAD!Oncogenes --> a cancer-causing gene, any of several mutant genesthat cause cells to exhibit rapid, uncontrolled proliferationDiscovered in tumor-causing virusesVery similar to normal genes in the body called proto-oncogenes(growth regulating genes)
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BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Truncated version of EGF receptorOncogenic form
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BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Tumor Suppressor Genes --> encode proteins that normallyrestrain cell division, mutation in one or more can lead to tumorgrowthp53 - mutated in 90% skin cancers, 50% all other cancersRb - mutated in retinoblastoma
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BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Tumor Progression
Adenomaous polyposis coli (TS gene)
Ras (oncogene)
Deleted colon carcinoma (TS gene)
p53 (TS gene)
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BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Programmed Cell Death (Apoptosis) --> cell brings about its owndeath and lysis, signaled from outside or programmed in its genes,by systematically degrading its own macromoleculesWhen?Development of embryo (fingers)Anti-self antibodies presentMenstruationStressed cells (virus-infected to prevent infection, heat, UV light)
Mutation to any of theseproteins can lead to cancers