1. Receptors and Signalling

2. Types of receptors... 1.Ion channels 2.Intracellular 3.Intrinsic enzyme activity 4.Soluble protein kinases 5.G-protein linked

3. Intrinsic enzyme activity 2 examples – Serine/threonine kinases – Tyrosine kinases

4. Serine/threonine kinases 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/threonine kinase

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... Guanylate cyclase – This is your classic VASODILATOR cascade one Clinical relevance question wise  – Blood pressure – Angina – Erections

11. Guanylate cyclase For blood pressure where Atrial naturitic peptide ANP is released  – Activates guanylate cyclase – 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. Guanylate cyclase 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 guanylate cyclase 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