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Receptors and Signalling

Receptors and Signalling . Types of receptors. Ion channels Intracellular Intrinsic enzyme activity Soluble protein kinases G-protein linked . Intrinsic enzyme activity . 2 examples Serine/ threonine kinases Tyrosine kinases. Serine/ threonine kinases.

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Receptors and Signalling

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  1. Receptors and Signalling

  2. Types of receptors... • Ion channels • Intracellular • Intrinsic enzyme activity • Soluble protein kinases • G-protein linked

  3. Intrinsic enzyme activity • 2 examples • Serine/threoninekinases • Tyrosine kinases

  4. Serine/threoninekinases • These have an ANTI-PROLIFERATIVE to the cell in general • Work through SMAD proteins Ligands: • Transforming growth factor B-like TGF-B1 • Activins • Bone morphogenetic proteins BMPs

  5. Ser/thr cascade • Inhibitory growth factor binds to receptor • Binding causes the receptor to dimerise • Activated receptor can now phosphorylate SMAD proteins • SMAD-P now joins with co-SMAD and can travel to the nucleus • Talks with some transcription factors and allows the transcription of the right genes

  6. Serine/threoninekinase

  7. Tyrosine kinases • These have a PROLIFERATIVE effect on the cell in general • Works through Ras Ligands: • Over 50 identified • Lots of growth factors GFs • Insulin

  8. Tyr cascade • Growth factor binds to the receptor • Binding causes the dimerisation of the receptor • Activated receptors now able to phosphorylate themselves • Receptor-P now able to bind the adapter molecule carrying Ras-GDP (inactive) • Nucleotide exchange occurs  GDP swopped for GTP = Active Ras

  9. Tyrosine kinase

  10. There is another receptor with intrinsic enzyme activity he talks about... • Guanylatecyclase • This is your classic VASODILATOR cascade one Clinical relevance question wise  • Blood pressure • Angina • Erections

  11. Guanylatecyclase • For blood pressure where Atrial naturitic peptide ANP is released  • Activates guanylatecyclase • Causes conversion of GTP to cGMP • cGMP activates protein kinase G PKG • PKG causes • Vasodilation • Increased sodium and urine production (getting rid of fluid to lower blood pressure) • Phosphorylation of sodium channels to reduce reabsorbtion  again making more urine to be lost, lowers blood pressure

  12. Guanylatecyclase • This time using ANGINA as the issue  • As a treatment for this the patient can use a GTN spray – which basically gets Nitric oxide (NO) into the body • NO activates guanylatecyclase and causes the same cascade as before • GTP  cGMP  PKG  vasodilation

  13. As always, just give us an email if something isn’t clear/need more pointers!! xxx

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