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Lecture 3

Lecture 3 Receptors and signalling.docx

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Michelle French

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Lecture 3: Receptors and signalling October-24-12 1:06 PM Hormone signalling • Hormone binds to receptor (either inside the cell or in the plasma membrane) • Changes the conformation and activity of the receptor • Alters the activity of intracellular signal pathways • Leads to changes in synthesis of target proteins and/or modification of existing target protiens • Hydrophobic hormones may also have extracellular receptors (in membrane) Receptor characteristics • Large proteins • Families • Can be multiple receptors for one ligand or more than one ligand for a receptor • Variable number in target cell (~500-100,000) • Activated and inhibited (either activation or inhibition) • Located in cell membrane, cytoplasm, nucleus • High affinity • Saturable • Specific • Reversible (binding is non covalent, can diffuse away) o Shown by experiment o Labelled and unlabelled steroid concentration with androgens and estrogens o How much of the non-labelled stuff we have to bring in before the labelled stuff is kicked off o Also can tell that the receptor in question is an androgen receptor because more affinity for them o Some of the estrogen can bind because it has a similar structure, but they are unphysiological concentrations of estrogen Types of receptors • Intracellular receptors (bind lipid soluble hormones) o Cytosolic and nuclear • Directly alter gene transcription (genomic effects) • Lipophilic messenger diffuses into the cytosol • Either binds to cytoplasmic receptor or goes into the nucleus where it binds to a nucleic receptor. • Hormone receptor complex (changes conformation to bind to HRE) • Hormone response element (HRE) • mRNA transcribed • mRNA leaves cell through nuclear pore to code for proteins • When HRE binds, other activators/repressors of transcription are recruited and it is either increased or decreased • Not all hormones have HRE • It takes time for synthesis of protein through this method • Plasma membrane receptors o G protein coupled receptors • Most common signalling pathways • Many different types fo G proteins: Gs, Gi, Gq etc • Targets  Adenylyl cyclase (Gs activates, Gi inhibits)  Phospholipase C  Guanylyl cyclase  Ion channles • Pathway (Gs activates adenylyl cyclase)  Gs inactive, bound to GDP  Messenger bonds to receptor  G protein binds to GTP, GDP kicked off  Noe active  Alpha subunit activates adenylyl cyclase  ATP -> cAMP  cAMP activates Protein kinase - A (PK-A)  PK-A phosphorylates protein  Response in cell • cAMP formation and breakdown • Pathway )Gq activa
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