《生物技术药物》之促红细胞生成素课件.pptVIP

各论;促红细胞生成素;;The JAK-STAT system consists of three main components: (1) a receptor (2) Janus kinase (JAK) and (3) Signal Transducer and Activator of Transcription (STAT). Many JAK-STAT pathways are expressed in white blood cells, and are therefore involved in regulation of the immune system. JAKs, which have tyrosine kinase activity, bind to some cell surface cytokine receptors. The binding of the ligand to the receptor triggers activation of JAKs. With increased kinase activity, they phosphorylate tyrosine residues on the receptor and create sites for interaction with proteins that contain phosphotyrosine-binding SH2 domains. STATs possessing SH2 domains capable of binding these phosphotyrosine residues are recruited to the receptors, and are themselves tyrosine-phosphorylated by JAKs. These phosphotyrosines then act as binding sites for SH2 domains of other STATs, mediating their dimerization. Different STATs form hetero- or homodimers. Activated STAT dimers accumulate in the cell nucleus and activate transcription of their target genes. STATs may also be tyrosine-phosphorylated directly by receptor tyrosine kinases, such as the epidermal growth factor receptor, as well as by non-receptor tyrosine kinases such as c-src.;Type I cytokine receptors, whose members have certain conserved motifs in their extracellular amino-acid domain. The IL-2 receptor belongs to this chain, whose γ-chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of Severe Combined Immunodeficiency (X-SCID). Type II cytokine receptors, whose members are receptors mainly for interferons. Immunoglobulin (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body Tumor necrosis factor receptor family, whose members share a cysteine-rich common extracellular binding domain, and includes several other non-cytokine ligands like receptors, CD40 , CD27 and CD30, besides the ligands on which the family is named (