医学细胞生物学课件：9 signaling.pptVIP

4.4 Wnt pathway Ligands: Secreted Wnt (mammals), Wg (Drosophila). Receptors: Frizzled (Fz) with seven transmembrane ? helices; associated with memberane–bound LDL receptor-related protein (LRP) required for receptor activity Signal transduction: Assembly of multiprotein complex at membrane that inhibits the proteasome-mediated proteolysis of cytosolic ?–catenin transcription factor, resulting in its accumulation Basic function: cell differentiation, cell proliferation and determination of cell fate Wnt signaling pathway Ligand: Wnt Receptor: LRP+Frizzled APC, adenomatous polyposis coli; ?-cat, ?-catenin; CBP, CREB-binding protein; CK, casein kinase; DKK, Dickkopf; DSH, Dishevelled; GBP, GSK3-binding protein; GSK, glycogen synthase kinase; LRP, LDL-receptor-related protein; P, phosphorylation; sFRP, secreted Frizzled-related protein; TCF, T-cell factor. Nat Rev Genetics 2004, 5, 689 Wnt pathway and diseases Nat Rev Genetics 2004, 5, 689 Overview of cell surface receptors 5. Intracellular receptor --Nitric oxide pathway Ligands: Nitric oxide. Receptors: NO receptor Signal transduction: Generation of cGMP Basic function: Vasodilation and neurotransmitter Regulation of contractility of arterial smooth muscle by NO and cGMP NO pathway in physiology and pathology Cardiovascular diseases Neurological diseases: Brain ischemia and chronic degenerative diseases of the nervous system Erectile dysfunction (impotence): Sildenafil, popularly known by the trade name Viagra, stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis. The Nobel Prize in Physiology or Medicine 1998 Robert F. Furchgott Louis J. Ignarro Ferid Murad for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system 6. Intracellular receptor -- Nuclear receptor pathway Ligands: steroid hormones, thyroxine, retinoid acids and fatty acid etc. Receptors: Highly conserved DNA-binding domain, somewhat conserved hormone