The ErbB kinase domain: structural perspectives into kinase activation and inhibition.

摘要: Epidermal growth factor receptor (EGFR) and its family members, ErbB2, ErbB3 ErbB4, are tyrosine kinases which send signals into the cell to regulate many critical processes including development, tissue homeostasis, tumorigenesis. Central signaling of these receptors is their intracellular kinase domain, activated by ligand-induced dimerization phosphorylates several residues in C-terminal tail. The phosphorylated tail then recruits other molecules relays signal downstream pathways. A model autoinhibition, activation feedback inhibition mechanisms for ErbB domain has emerged from a number recent structural studies. Meanwhile, clinical studies have revealed relationship between specific mutations responsiveness inhibitor drugs. We will review regulation discuss binding specificity inhibitors effects found cancer patients perspective.