信号转导2－生化课08演示文稿.ppt

* 肠 腔 Gs CT 霍乱 (Cholera) AC cAMP ↑ ↑ ↑ Cl- H2O Na+ CT：Cholera Toxin * 三、多环节信号转导异常与疾病 ㈠ 肿瘤 1. 促细胞增殖的信号转导过强 ⑴ 生长因子产生增多 ⑵受体的改变 生长因子受体表达异常增多 突变使受体组成型激活 ⑶细胞内信号转导蛋白的改变 如Ras突变 * 2. 抑制细胞增殖的信号转导过弱 生长抑制因子受体减少、丧失 受体后信号转导通路异常 细胞的生长负调控机制减弱或丧失 * Oncogene-encoded defective EGF receptor * GEF：Guanine nucleotide Exchange Factor GAP：GTPase Activating Protein Activation of Ras protein * GEF：Guanine nucleotide Exchange Factor GAP：GTPase Activating Protein Mutation of Ras constitutive activation * 肿瘤形成必须是在单个细胞中发生多重遗传突变 单个癌基因激活和抑癌基因失活不足以引起肿瘤细胞的显著扩增， 因为细胞对凋亡的易感性也同时增加；凋亡抑制是肿瘤细胞能够生长到足以威胁宿主所必须的；例如： Rb的失活仅会促进p53依赖的凋亡，但不会引起肿瘤，除非细胞的凋亡过程被抑制； Apoptosis and oncogenesis * 3.3.3 Oncogenes, Tumor Suppressor Genes (TSGs), and Programmed Cell Death Oncogenes: encode defective signaling proteins ( e.g., growth factors, receptors, G proteins, protein kinases, or transcription regulators), continually giving the signal for cell division; TSG: encode regulatory proteins; normally inhibit cell division; mutations in these genes are genetically recessive Cancer: the result of an accumulation of mutations in oncogenes and TSGs. * From normal epithelial cell to cancer * 细胞信号转导调控与疾病防治 Regulation of cellular signals in prevention treatment of diseases 以信号转导蛋白为靶分子对疾病进行防治 * STI571 as a paradigm (范例）for cancer therapy In 1960, described the presence of a consistent chromosomal abnormality in CML（一种白血病)，so-called Philadelphia chromosome (Ph) A reciprocal translocation between the long arms of chromosomes 9 and 22, t(9:22)(q34;q11), The molecular consequence of this event is the generation of a chimeric bcr-abl gene (22:9) * The tyrosine kinase activity of Bcr-Abl stimulates a variety of signaling pathways, leading to alterations in survival properties of cells * STI571 an Abl-specific tyrosine kinase inhibitor Before the discovery of this drug, most CML patients died within 6 month * * * 我从事的研究领域是免疫学，感染是影响人类生存的主要疾病，清除感染依赖于有效的免疫防御功能， 吞噬细胞是人体防御入侵病原的第一道防线，能有效的摄取并杀灭病原（图）， 但病原菌从进化过程中获得多种致病