signal transduction (2)

PPT 34 стр. 6,1 МБ Бесплатная загрузка

34 стр.

FaylHub.uz

Скачать через Telegram

Размер 6,1 МБ

Тип файла PPT

Страницы 34

Обновлено Дек 2025

Предварительный просмотр (5 стр.)

Прокрутите вниз 👇

1 / 34

powerpoint presentation signal transduction (2) dr. fiona murray school of medical sciences fmurray@abdn.ac.uk * reading/resource rang, dale and ritter. rang and dale’s pharmacology 8th edition: ch3 * outline – lecture 4 overview of signal transduction types of receptors ligand-gated ion channels g protein–coupled receptor g proteins effectors of g proteins second messengers (camp, ip3, dag, rhoa) tyrosine kinase linked receptors nuclear/intracellular receptors general summary * marinissen et al., trends pharmacol sci. (2001); 22(7), 368 g protein-coupled receptor signaling * targets for g proteins adenylyl cyclase membrane bound enzyme (gαs, gαi) phospholipase c membrane bound enzyme (gαq) rhogef (gα12/13) ion channels (all) second messenger – cyclic 3’, 5’ adenosine monophosphate (camp) second messengers - inositol phosphate (ip3) and diacylglycerol (dag) ca2+, k+ channels second messenger - rhoa βγ – adenyly cyclase, ion channels, gpcr kinase, pi3kγ, plcβ α these direct effectors feed into many other pathways, such as the mitogen-activated protein …

2 / 34

mp formation atp acs camp activators: forskolin, colforsin daropate hydrochloride (nkh447, japan) * phosphodiesterases (pdes)- camp degradation camp 5’amp pdes 11 pdes characterized pdes differ in: sequence substrate specificity (camp/cgmp) regulation tissue/cell distribution clinically used inhibitors –sildenafil (pde5, cgmp), roflumilast (pde4, camp), theophylline (non-selective, both) * camp pde ac ?? the camp pathway: formation vs. degradation camp pde ac ?? * downstream mediators of camp na+, k+ ca2+ * protein kinase a pka phosphorylates proteins and also regulating transcription (creb) many levels of –ve feedback (*) * * * * gαs-coupled gpcr desensitization (β2-adrenoceptor) hypothetical time course of camp accumulation “resting” steady state camp levels in cell -agonist increases camp to a steady state (synthesis = degradation) camp time β2-ar desensitization 2 1 3 4 3. decreased -receptor-g protein interaction ( camp synthesis, -arrestin) 4. down-regulation of receptor number and increased pde activity (hydrolysis) * actions of increased camp increases …

3 / 34

including cell growth and metabolism gpcr-gq-plc-ip3/dag * phospholipase c phosphatidyl inositol 4,5 bisphosphate (pip2) inositol 1,4,5 triphosphate (ip3) diacylglyercerol (dag) increases in intracellular ca2+ activation of protein kinase c phospholipase cβ (plc) phosphatidyl inositol cycle pip2:phosphatidylinositol biophosphate, ip3: inositol triphosphate, dag: diacylglycerol, pa: phosphatidic acid, ip: inositol 1-phosphate, plc: phospholipase c ip3 - releases intracellular ca++ dag - activates protein kinase c pip2 ip3* dag** ip pa plc phosphatases kinases * ip3 and ca2+ release gq plcβ dag ip3 ca2+ ca2+ cellular responses er ligand ip3r intracellular ligand gated ion channel on endoplasmic reticulum – mobilisation of ca2+ from intracellular stores ecf r ip3r ip4?? * actions of increased intracellular calcium muscle contraction (cardiac, skeletal and smooth muscle) (α1-adrenoceptors, muscarinic receptor, endothelin receptor) hormone release immune response – increases t cell proliferation release of neurotransmitters increased force of cardiac muscle contraction triggers migration of pkc to membrane * actions of …

4 / 34

cilitates gdp-gtp exchange at rhoa: - activates rho-associated protein kinase (rock) * actions of increased rhogef activity contraction of smooth muscle proliferation of smooth muscle angiogenesis migration synaptic remodelling one gene…..one gpcr…..one g protein…..one response g protein-coupled receptor signaling 5-ht * second messengers and protein phosphorylation many receptor-effector interactions result in kinase activity kinase enzymes phosphorylate substrate examples: protein kinase a (pka) protein kinase c (pkc) cam kinase g protein-coupled receptor kinases (grk) tyrosine kinase kinases have different substrate specificities * phosphorylation/dephosphorylation protein protein -p atp adp adp atp kinase atp synthase / phosphatase * second messengers and protein phosphorylation * activation of adenylyl cyclase ceases. similar amplification probably occurs in signaling from receptors coupled to other g proteins and some other types of receptors whose activa- tion induces synthesis of second messengers. a second level of amplification is illustrated by the camp-mediated stimulation of glycogenolysis. as we just discussed, …

5 / 34

inase, and glycogen phosphorylase—are in a 1:10:240 ratio, which dramatically illustrates the amplifica- tion of the effects of epinephrine and camp. although such a cascade may seem overcomplicated, it not only greatly amplifies an external signal but also allows an entire group of enzyme-catalyzed reactions to be coordi- nately regulated by a single type of signaling molecule. in ad- dition, the multiple steps between stimulus and final response offer possibilities for regulation by other signaling pathways, thereby fine-tuning the cellular response. we will encounter other examples of cascades in signaling pathways discussed in the next chapter. several mechanisms regulate signaling from g protein–coupled receptors several factors contribute to termination of the response to hormones recognized by "-adrenergic receptors and other re- ceptors coupled to gs. first, the affinity of the receptor for hormone decreases when the gdp bound to gs# is replaced with a gtp following hormone binding. this increase …

Хотите читать дальше?

Скачайте все 34 страниц бесплатно через Telegram.

Скачать полный файл

О "signal transduction (2)"

powerpoint presentation signal transduction (2) dr. fiona murray school of medical sciences fmurray@abdn.ac.uk * reading/resource rang, dale and ritter. rang and dale’s pharmacology 8th edition: ch3 * outline – lecture 4 overview of signal transduction types of receptors ligand-gated ion channels g protein–coupled receptor g proteins effectors of g proteins second messengers (camp, ip3, dag, rhoa) tyrosine kinase linked receptors nuclear/intracellular receptors general summary * marinissen et al., trends pharmacol sci. (2001); 22(7), 368 g protein-coupled receptor signaling * targets for g proteins adenylyl cyclase membrane bound enzyme (gαs, gαi) phospholipase c membrane bound enzyme (gαq) rhogef (gα12/13) ion channels (all) second messenger – cyclic 3’, 5’ adenosine monophosphate (camp) ...

Этот файл содержит 34 стр. в формате PPT (6,1 МБ). Чтобы скачать "signal transduction (2)", нажмите кнопку Telegram слева.

Теги: signal transduction (2) PPT 34 стр. Бесплатная загрузка Telegram