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Cell signalling 2
- 4. Signal Reception: G Protein-Coupled Receptors
- 18. Another Receptor – G Protein Cycle
- 19. Structure, function and mechanisms of G-Proteins
- 21. 1994 Nobel Prize in Medicine, Alfred Gilman and Martin Rodbell, for their „discovery of G-Proteins and the role of these proteins in signal transduction in cells.“
- 22. G-Protein = Guanine-nucleotide binding protein (GNBD) Guanine Ribose Phosphates 1 2 5 4 3 α 1 3 4 2 6 5 7 8 9 Guanosine Ester Anhydride Guanosine-triphosphate - GTP
- 37. & subunits have covalently attached lipid anchors that bind a G-protein to the plasma membrane cytosolic surface. Adenylate Cyclase (AC) is a transmembrane protein, with cytosolic domains forming the catalytic site. The subunit of a G-protein ( G ) binds GTP , & can hydrolyze it to GDP + P i .
- 42. Fig 15.3 The G Protein Cycle
- 46. G Protein-Linked Receptors note how activation is reversible
- 47. G Protein-Linked Receptors the more ligand binding, the more K + in cytoplasm
- 53. How G-protein-coupled receptors work (1) extracellular space cytosol heterotrimeric G-protein ‘ 7TM’ - receptor GDP GDP GTP Ligand N
- 54. How G-protein-coupled receptors work (2) inactive GDP P active N GTP N
- 55. How G-protein-coupled receptors work (3) ATP inactive inactive active cAMP cAMP Protein kinase A Phosphorylation of multiple target proteins active Adenylate cyclase GTP
- 56. Some G-proteins are inhibitory -Adrenoceptor 2 -Adrenoceptor AC active AC inactive s GTP i GTP
- 57. -Subunits of G proteins may have regulatory activity, too Muscarinic (M 2 ) acetylcholine receptor K ir AC inactive K + i GTP
- 58. G -proteins regulate diverse effector systems q phospholipase C PIP 2 IP 3 + DAG protein kinase C phosphorylation of multiple proteins Ca ++ ER t cGMP phosphodiesterase cGMP s adenylate cyclase protein kinase A cAMP i1 adenylate cyclase protein kinase A cAMP
- 59. Many transmitters have multiple GPCR with different downstream signaling mechanisms Norepinephrine, 1 IP 3 + DAG epinephrine 2 cAMP 1 , 2 cAMP Dopamine D 2 - D 4 cAMP D 1 , D 5 cAMP Acetylcholine IP 3 + DAG 2 , M 3 cAMP
Editor's Notes
- D3 is somewhat mysterious – some references say it drops cAMP. Need to find out more about that.