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.“
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 .
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
60.
Notes de l'éditeur
D3 is somewhat mysterious – some references say it drops cAMP. Need to find out more about that.