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Lecture 11

BIO241 Lecture 11

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Darrel Desveaux

BIO241 Lecture 11 Cell Communication II - *57490L3 .and subunits anchored in the lipid bilayer, inactive form bound to GDP, activated receptor induces conformational change in trimeric protein and GDP exchanged for GTP, GTP concentration in cytosol naturally high, .and - units dissociate - .8:-:3L99,7J09,denylyl cyclase, one .8:-:3L9 activates one adenylyl cyclase which produces many cAMP which activates PKA (usually inactive in the cell) o PKA made of two types of subunits: 2 catalytic: carry out P-ation and 2 regulatory: keep catalytic units in inactive form o catalytic subunits P-ate specific substrate proteins o cAMP binds to regulatory subunits conformational change in regulatory subunits that dissociate with catalytic subunits, activating them o PKA effects are transient, phosphatases deP-ate target proteins o e.g. glycogen: adrenalin (ligand), produced in adrenal gland as a stress response to promote glucose release to provide energy, will activate PKA via G proteins Promote breakdown off glycogen Inhibit glycogen synthesis o Glycogen is broken down into glucose-1-P glucose-6-P via glycolytic pathway and is trapped in the cell o PKA P-ates glycogen phosphorylase kinase which P-ates glycogen phosphorylase which acts to break glycogen down, PKA also P-ates to inhibit glycogen synthase (which acts to synthesize glycogen) o Rapid response, immediate effect but can be slow in different cell types because of transcription factors cAMP responsive elements (CRE) in DNA is bound by CREB (binding protein) transcription factor activated PKA will enter nucleus to P-ateactivate CREB which recruits CBP (coactivator) transcription of target genes in the liver, e.g. glucose-6-phosphatase which deP-ates glucose-6-P to glucose so that it can be released from the liver into the blood (slow process) - Enzyme-linked cell surface receptors o Membrane spanning proteins, extracellular ligand-binding domain, intracellular domain has enzyme activity, e.g. kinase domains o Receptors inactive state is monomeric, ligand binding dimerization of receptors and activates catalytickinase domain or recruits and activates associated enzyme to receptor o Receptor tyrosine kinases (RTK): ligands (growth factors, hormones) pro- life signals, responses (cell proliferation, differentiation, survival)
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