《生物技术药物》之促红细胞生成素.pptVIP

c-Jun N-terminal kinases (JNKs) The c-Jun N-terminal kinases consist of ten isoforms derived from three genes: JNK1 (four isoforms), JNK2 (four isoforms) and JNK3 (two isoforms) JNK, by phosphorylation, modifies the activity of numerous proteins that reside at the mitochondria or act in the nucleus. Downstream molecules that are activated by JNK include c-Jun, ATF2, ELK1, SMAD4, p53 and HSF1. The downstream molecules that are inhibited by JNK activation include NFAT4, NFATC1 and STAT3. By activating and inhibiting other small molecules in this way, JNK activity regulates several important cellular functions including cell growth, differentiation, survival and apoptosis. 血小板衍生生长因子 Plateletd-erived growth factor，PDGF从血小板中发现，在损伤早期从血小板α颗粒释放出来，启动并加速组织创伤修复， 主要由血小板合成，在组织受到损伤时巨噬细胞、血管平滑肌细胞、成纤维细胞、内皮细胞、胚胎干细胞等也可以合成并释放PDGF。 结构：是靠二硫键相连的A、B两条多肽链组合成的二聚体。A链125/110个氨基酸，3个二硫键；B链109个氨基酸，3个二硫键 生物学特性： 刺激血管平滑肌细胞、成纤维细胞、胶质细胞的分裂增生；诱导巨噬细胞与成纤维细胞的游走，对中性粒细胞、平滑肌细胞、成纤维细胞有趋化性；具有缩血管活性；诱导基因表达。 临床：伤口愈合 MAPK pathway The adaptor protein Grb2 forms a complex with Sos by the Grb2 SH3 domain. Grb2 (or) the Grb2/Sos complex is recruited to the membrane by the Grb2 SH2 domain binding to activated PDGFR-bound SHP2 (Also known as PTPN11, a cytosolic PTP), thereby allowing interaction with Ras and the exchange of GDP for GTP on Ras. Whereas the interaction between Grb2 and PDGFR occurs through interaction with the SHP2 protein, Grb2 binds to activated EGFR through Shc, another adaptor protein that forms a complex with many receptors via its PTB domain. Once activated, Ras interacts with several proteins, namely Raf. Activated Raf stimulates MAPK-kinase (MAPKK or MEK) by phosphorylating a Ser residue in its activation loop. MAPKK then phosphorylates MAPK (ERK1/2) on T and Y residues at the activation-loop leading to its activation. Activated MAPK phosphorylates a variety of cytoplasmic substrates, as well as transcription factors, when translocated into the nucleus. MAPK family members have been found to regula