信号转导1－生化课08幻灯片.ppt

* Epinephrine triggers a series of reactions in hepatocytes in which catalysts activate catalysts, resulting in great “amplification” of the signal x 分子 10 ,000 x 分子 * PKA regulates a number of enzymes The proteins phosohorylated by PKA share a region of sequence similarity around the Ser or Thr residue that undergoes phosphorylation, a sequence that marks them for regulation by PKA. The catalytic site of PKA interacts with several residues near the Thr or Ser residue in the target protein, which define the substrate specificity. * * Desensitization of the PKA system 1 desensitizing β-Adrenergic Receptor 2 degrading the second messager * Gsbg recruits bARK to the membrane, where it phospho- Ser at the C-terminus of Recpt. barr binds to the pi- C-terminus of Recpt. Receptor-arrestin complex enters the cell by endocytosis. * β-Arrestin uncouples receptor from its G protein and brings together 3 enzymes of MAPK cascade. (One stimulus triggers two distinct pathways: the path activated by G protein and MAPK cascade) * degrading the second messager * The Protein kinase C (PKC) System Two intracellular 2nd messengers are produced in the hormone-sensitive phosphatidylinositol system: Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Both contribute to the activation of PKC. By raising cytosolic [Ca2+], IP3 also activates other Ca2-dependent enzymes; thus Ca2+ also acts as a second messenger * * Calcium Is a Second Messenger in Many Signal Transductions Normally, [Ca2]i is ~100 nM (而细胞外：1 mM) Hormonal, neural, or other stimuli cause either an influx of Ca2+ into the cell through specific Ca2+ channels in the plasma membrane or the release of Ca2+ from ER or mitochondria, Changes in [Ca2]i are detected by Ca2+-binding proteins that regulate a variety of Ca2-dependent enzymes-Calmodulin (CaM) * Regulation of transcription by steroid hormones Steroid receptor * * * * * * * * * * * * asymmetric ion-distribution Resting potential * pump and ion leak channels