Tyrosine kinase signalling Tyrosine kinase structure dimeric transmembrane protein intrinsic kinase activity phosphorylated receptor can bind protein called insulin receptor substrate (IRS) is a scaffold protein Pathway hormone binds to receptor receptor is dimerized auto cross-phosphorylation of intracellular domain of the dimerized receptor IRS binds phosphorylated domian IRS is phosphorylated on SH2-domains several enzymes bind phosphorylated SH2-domians phosphatases login to view 1 more bullet kinases login to view 1 more bullet G proteins login to view 3 more bullets Examples insulin, PDGF, EGF receptors sensitization via PPAR-gamma G protein signalling G-protein structure trimeric enzyme α, β, γ login to view 2 more bullets Pathway hormone binds to receptor:G-protein complex on cell membrane GDP bound to inactive α-subunit is exchanged for GTP α-subunit now active can be inhibitory (Gi) or stimulatory (Gs, Gq) is released from β, γ subunits can act as 2 different effector mechanisms cAMP pathway login to view 11 more bullets PIP2 pathway login to view 5 more bullets GTP eventually hydrolyzed to GDP and α-subunit becomes inactive Examples cAMP = glucagon, epinephrine (β, α2) PIP2 = vasopressin, epinephrine (α1) full list given in G-protein-linked 2nd messengers topic cGMP signalling Pathway hormone binds to receptor on cell membrane there is also a soluble receptor in the cytoplasm receptor has intrinsic guanylate cyclase activity GTP → cGMP login to view 2 more bullets no G protein required Examples ANF → cell membrane receptor NO → diffuses across cell membrane and binds soluble receptor mechanism for pharmacologic nitrates (nitroprusside, nitroglycerine)