tailieunhanh - Tìm hiểu về Tyrosine

Tài liệu Tìm hiểu về Tyrosine với các nội dung: Khám phá thụ thể Tyrosine kinase, các học thuyết về sự kích hoạt thụ thể Tyrosine Kinase, chi tiết sự hoạt hóa dimer hóa tysosine, chi tiết quá trình tự phosphoryl hóa tyrosine, chất ức chế RTK (Receptor Tyrosine Kinase), thụ thể insulin. | Nhóm thụ thể Tyrosine Kinase Tyrosine kinase receptors Distinct mechanisms of small-molecule inhibitors and monoclonal antibodies for targeting receptor tyrosine kinases in cancer cells. a Epidermal growth factor receptor EGFR and receptor tyrosine kinase RTK -dependent growth signalling in cancer cells. The extracellular region of EGFR consists of four domains the ligand-binding domains L1 and L2 and the cysteine-rich domains CR1 and CR2 and the C-terminal domain of EGFR contains six tyrosine residues Y only two are depicted here for simplicity . Following the activation of EGFR by ligand binding or ligand-independent dimerization the Ras-Raf-MEK-MAPK pathway is activated through the growth factor receptor-bound protein 2 GRB2 -SOS complex. EGFR-mediated signalling also activates the phosphatidylinositol 3-kinase PI3K -AKT pathway which contributes to anti-apoptotic effects of EGFR activation. Additionally signal transducer and activator of transcription Stat proteins STAT1 STAT3 and STAT5 are also activated. The coordinated effects of these EGFR downstream signalling pathways lead to the induction of cellular responses including proliferation differentiation cell motility adhesion and angiogenesis. The deregulation of EGFR-mediated signalling in some cancer cells leads to aberrant proliferation invasion metastasis and neovascularization. 9 b Small-molecule tyrosine kinase inhibitors TKIs such as gefitinib function as ATP analogues and inhibit EGFR signalling by competing with ATP binding within the catalytic kinase domain of RTKs. As a result the activation of various downstream signalling pathways is blocked. Each TKI has a different selectivity for RTKs and some are dual- or multi-selective which might provide a therapeutic advantage. c By contrast therapeutic monoclonal antibodies mAbs bind to the ectodomain of the RTK with high specificity for example cetuximab binds to the L2 domain of EGFR and thereby inhibits its downstream signalling by triggering .