细胞信号传导-精美英文课件-cellular signal transduction pathway.pptVIP

cellular signal transduction pathway G protein-mediated signal transduction Tyrosine protein kinase-mediated signal transduction Guanylate cyclase signal transduction pathway Nuclear receptor-mediated signal transduction Three subunits The sequence of events by which a hormone activates cAMP signaling: 1. Initially Ga has bound GDP, and αβ γ subunits are complexed together. 2. Hormone binding to a 7-helix receptor (GPCR) causes a conformational change in the receptor that is transmitted to the G protein. The nucleotide-binding site on Ga becomes more accessible to the cytosol, where [GTP] [GDP]. Ga releases GDP binds GTP (GDP-GTP exchange). 3. Substitution of GTP for GDP causes another conformational change in Ga. Ga-GTP dissociates from the inhibitory βγ complex can now bind to and activate Adenylate Cyclase. 4. Adenylate Cyclase, activated by Ga-GTP, catalyzes synthesis of cAMP. 5. Protein Kinase A (cAMP Dependent Protein Kinase) catalyzes phosphorylation of various cellular proteins, altering their activity. Protein Kinase A (cAMP-Dependent Protein Kinase) transfers Pi from ATP to OH of a Ser or Thr in a particular 5-amino acid sequence. Protein Kinase A in the resting state is a complex of: 2 catalytic subunits (C) 2 regulatory subunits (R). R2C2 The domain of (R) binds to the active site of (C), blocking its activity. When each (R) binds 2 cAMP, a conformational change causes (R) to release (C). Each catalytic subunit can then catalyze phosphorylation of Ser or Thr on target proteins. R2C2 + 4 cAMP ? R2cAMP4 + 2 C Effects of PKA Ser/Thr残基磷酸化 （1）对代谢的调节作用 肾上腺素调节糖原分解 （2）对基因表达的调节作用 cAMP应答元件（CRE）基因调控区 cAMP应答元件结合蛋白（CREB）反式作用因子 PKA的催化亚基进入细胞后使CERB特定的Ser/Thr磷酸化，形成同源二聚体，结合DNA，激活转录 Many enzymes are regulated by covalent attachment of phosphate, in ester linkage, to the side-chain hydroxyl group of a particular amino acid residue (serine, threonine, or tyrosine). A protein kinase transfers the terminal phosphate of ATP to a hydrox