清华本科课件《生物化学》Biosignaling1 188202049.pptVIP

Mitogen-activated protein kinase In the hunt for tyrosine kinase substrates, a superfamily of protein kinases were identified around 1990. They were initially demonstrated to phosphorylate microtubule-associated protein (MAP); now the acronym remains, but with a different meaning: mitogen-activated protein kinase. (Mitogens: the substances that induce mitosis) They are dually phosphorylated by their upstream kinases (MAP kinase kinase) on both Ser/Thr and Tyr. Receptor tyrosine kinase Epidermal growth factor receptor Platelet-derived growth factor receptor Fibroblast growth factor receptor Kinase domains Ligand binding domains Insulin receptor Plant receptor kinases Arabidopsis genome has 417 receptor kinase genes!!! LRR-type CR4-like WAK type S-domain type Lectin type BR signaling Epidermal cell Function Self-incompatible Fuction differentiation unknown pollination unknown Meristem organization Pathogen defense ~ 1/3 of the proteins in a cell are phosphorylated at any given time Moreover, many of the signaling proteins controlled by phosphorylation are themselves protein kinases These are organized in phosphorylation cascades One protein kinase , activated by phosphorylation, phosphorylates the next protein kinase in the sequence, and so on, relaying the signal onward Phosphorylation cascades Activation of glycogen synthase by insulin Activation of glycogen synthase by insulin PI-3K: Phosphoinositide 3-kinase PIP2: Phosphatidylinositol 4,5-bisphosphate PIP3: Phosphatidylinositol 3, 4,5-triphosphate PKB: Protein kinase B + PIP2 Activation of glycogen synthase by insulin PKB: Protein kinase B GSK3: Glycogen synthase kinase 3 GS: Glycogen synthase Activation of glycogen synthase by insulin PKB: Protein kinase B GLUT4: Glucose transporter 4 Activation of glycogen synthase by insulin To preve