Biosignaling

Cells - receive and act on signalsSignal brings about response

Types of signals:Autocrine - acting on same cell that produces themParacrine - acting on nearby cellEndocrine - carried in bloodstream from producer cell to a distant target cell

Lots of signals but just a few evolutionarily conserved mechanisms to detect signals and transduce them into change in cell

Weak interactionsReceptor cell-specificHigh affinity of receptors for signalCooperativity

Biosignaling

Types of signal transducers

Biosignaling

I. 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

DesensitizationSpecificity

Biosignaling

I. Ligand-gated Ion Channel

Nicotinic Acetylcholine receptor

Acetylcholinesterase - enzyme that degrades the neurotransmitter acetylcholine. It is mainly found at neuromuscular junctions and cholinergic synapses in the central nervous system, where its activity serves to terminate synaptic transmission.

Acetylcholinesterase inhibitor - inhibits the break down of acetylcholine; occur naturally in venoms and poisons & used as weapons in the form of nerve agents (sarin); interrupt the breakdown of the neurotransmitters that signal muscles to contract, preventing them from relaxing

Biosignaling

II. Receptor Enzymes

Insulin ReceptorLigand-binding domain on extracellular surface of plasma membraneEnzyme active site on cytosolic side

nucleus

SpecificityAmplification(Phosphorylation)

Biosignaling

II. Receptor EnzymesInsulin Receptor

Biosignaling

III. G protein-coupled Receptors and Second Messengers-Adrenergic Receptor

a.k.a. AdrenalineRegulates metabolism in muscle, liver and fatBreakdown of glycogen and fat

Serpentine receptor - 7 transmembrane helices

SpecificityAmplification(Phosphorylation)

Biosignaling

III. G protein-coupled Receptors and Second MessengersEpinephrine

SpecificityAmplification

Biosignaling

IV. Steroid receptorsAct in nucleus to alter gene expressionSteroid hormones (estrogen, progesterone, cortisol, etc.) hydrophobicReceptors (proteins) and HREs (hormone response elements in DNA)

Biosignaling

IV. 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

Biosignaling

Oncogenes, Tumor Suppressor Genes, Programmed Cell Death

Tumors --> result of uncontrolled cell division - biosignaling gone BAD!Oncogenes --> a cancer-causing gene, any of several mutant genes that cause cells to exhibit rapid, uncontrolled proliferationDiscovered in tumor-causing virusesVery similar to normal genes in the body called proto-oncogenes (growth regulating genes)

Biosignaling

Oncogenes, Tumor Suppressor Genes, Programmed Cell Death

Truncated version of EGF receptorOncogenic form

Biosignaling

Oncogenes, Tumor Suppressor Genes, Programmed Cell Death

Tumor Suppressor Genes --> encode proteins that normally restrain cell division, mutation in one or more can lead to tumor growthp53 - mutated in 90% skin cancers, 50% all other cancersRb - mutated in retinoblastoma

Adenomaous polyposis coli (TS gene)

Ras (oncogene)

Deleted colon carcinoma (TS gene)

p53 (TS gene)

Biosignaling

Oncogenes, Tumor Suppressor Genes, Programmed Cell Death

Programmed Cell Death (Apoptosis) --> cell brings about its own death 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 these proteins can lead to cancers