第5章+细胞信号转导与肿瘤要点.ppt

Rb BRCA1 and BRCA2 General principles of cell communication Growth factor, receptor and cancer Signaling through enzyme-linked cell-surface receptors and cancer Wnt - β- catenin signaling pathway and cancer NF-kB- dependent signaling pathway and cancer Signaling through G-protein- coupled receptors (GPCRs) and cancer General principles of cell communication Normal metazoan cells control each other’s lives Our digestive tract begins with the mouth and stomach, continues with the small and large intestines, and ends with the colon. The life cycle of small intestinal enterocytes The wound-healing process The Src protein functions as a tyrosine kinase The first clues to how cell-to-cell signaling via growth factors came from biochemical analysis of the v-src oncogene and the protein that it specifies Src operates as a protein kinase Phosphorylation of a precipitating antibody molecular by Src Src phosphorylated certain tyrosine residues of its protein substrates More than 99% of the phosphoamino acids in normal cells are phosphothreonine or phosphoserine Phosphotyrosine constitutes as little as 0.05 to 0.1% of these cells’ total phosphoamino acids How did the phosphorylation of tyrosine residues result in cell transformation? Src and tumor The EGF receptor functions as a tyrosine kinase Epidermal growth factor (EGF), the first of the growth factors to be discovered Ability to provoke premature eye opening in newborn mice Have mitogenic effects when applied to a variety of epithelial cell(上皮细胞) types — EGF served as the ligand for its cognate receptor- the still-hypothetical EGF receptor (EGF-R) Subsequent sequencing efforts revealed overall sequence similarities among a variety of tyrosine kinases, many of which can function as oncoproteins Transphosphorylation underlies the operations of receptor tyrosine kinases Apparent autophosphorylation of the EGF receptor Receptor dimerization following ligand binding Alternative mechanisms of growth factor-induce