Biosignaling Cells - receive and act on signals

Biosignaling Cells - receive and act on signals

Biosignaling Cells - receive and act on signals Signal brings about response Types of signals: Autocrine - acting on same cell that produces them Paracrine - acting on nearby cell Endocrine - 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 interactions Receptor cell-specific High affinity of receptors for signal Cooperativity Biosignaling Types of signal transducers Biosignaling I. Ligand-gated Ion Channel

Nicotinic Acetylcholine receptor opens in response to neurotransmitter acetylcholine and to nicotine Found in neurons and muscle fibers Receptor = Allosteric protein Cooperative binding of Ach Desensitization Specificity 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 Biosignaling II. Receptor Enzymes

Insulin Receptor Ligand-binding domain on extracellular surface of plasma membrane Enzyme active site on cytosolic side Specificity Amplification (Phosphorylation nucleus Biosignaling

II. Receptor Enzymes Insulin Receptor Biosignaling III. G protein-coupled Receptors and Second Messengers -Adrenergic ReceptorAdrenergic Receptor a.k.a. Adrenaline Regulates metabolism in muscle, liver and Breakdown of glycogen and fat

Serpentine receptor - 7 transmembrane helices Specificity Amplification (Phosphorylation) Biosignaling III. G protein-coupled Receptors and Second Messengers Epinephrine Specificity

Amplification Biosignaling IV. Steroid receptors Act in nucleus to alter gene expression Steroid hormones (estrogen, progesterone, cortisol, etc.) hydrophobic Receptors (proteins) and HREs (hormone response elements in DNA) Biosignaling IV. Steroid receptors

Receptor for estrogen Breast cancer - some types need estrogen present for tumor growth Tamoxifen = antagonist of estrogen Tamoxifen competes with estrogen for binding to receptor Tamoxifen has no effect on gene expression like estrogen does RU486 = antagonist of progesterone Competes with prog for binding

to receptor Prog needed for proper implantation of fertilized ovum in 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 proliferation Discovered in tumor-causing viruses Very 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 recept Oncogenic form

Biosignaling Oncogenes, Tumor Suppressor Genes, Programmed Cell Death Tumor Suppressor Genes -Adrenergic Receptor-Adrenergic Receptor> encode proteins that normally restrain cell division, mutation in one or more can lead to tumor growth p53 - mutated in 90% skin cancers, 50% all other cancers Rb - mutated in retinoblastoma Adenomaous polyposis coli (TS gen

Ras (oncogene) Deleted colon carcinoma (TS gene p53 (TS gene) Biosignaling Oncogenes, Tumor Suppressor Genes, Programmed Cell Death Programmed Cell Death (Apoptosis) -Adrenergic Receptor-Adrenergic Receptor> cell brings about its own death and lysis, signaled from outside or programmed in its genes, by systematically degrading its own

macromolecules When? Development of embryo (fingers) Anti-self antibodies present Menstruation Stressed cells (virus-infected to prevent infection, heat, UV light) Mutation to any of these proteins can lead to cancers

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