信号转导1－生化课05课件.ppt

* * * synthesized in adrenal medulla; belongs to catecholamines (儿茶酚胺）; target cells include liver, skeletal muscle, heart muscle and adipose; released in response to acute stress Epinephrine 肾上腺素 signal Epinephrine 肾上腺素 signaling pathway cAMP Epinephrine 肾上腺素 signaling pathway (2) Activation of cAMP-dependent protein kinase (PKA) Inactive PKA: Regulatory (R) subunits: auto-inhibitory domains buried catalytic (C) subunits: substrate-binding sites blocked by R subunits R subunits: autoinhibitory domains buried Active PKA C subunits open substrate binding sites A catalytic subunit of PKA ATP Potent inhibitor peptide (PKI): Arg-Arg-Gln-Ala-Ile (consensus sequence recognized by PKA except Ala) 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 the serpentine receptor from its G protein and brings together the three enzymes of the MAPK cascade. (One stimulus triggers two distinct pathways: the path activated by G protein and MAPK cascade) The Protein kinase C (PKC) System Two intracellular second 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