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
BiosignalingTypes of signal transducers
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
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)
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
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)
BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Truncated version of EGF receptorOncogenic form
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
BiosignalingOncogenes, Tumor Suppressor Genes, Programmed Cell Death
Tumor Progression
Adenomaous polyposis coli (TS gene)
Ras (oncogene)
Deleted colon carcinoma (TS gene)
p53 (TS gene)
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