信号转导3-CST-RTK.pptx

Chapter 3 ;3.1 Receptor Enzymes;3.1 Receptor Enzymes;3.2 Receptor tyrosine kinases;The big family of Receptor Tyrosine Kinases ;Structure of RTKs;Dimerization of RTKs;Receptor domain architecture and receptor activation by EGF;Receptor domain architecture and receptor activation by EGF;Autophosphorylation of RTKs;Autophosphorylation of RTKs;Assembly of receptor signalling complexes;;Domain architecture of adaptor-, docking- and effector proteins;Different protein-protein interaction domains drive the assembly of receptor signalling complexes;Epidermal Growth Factor Receptor (EGFR);Epidermal Growth Factor Receptor (EGFR);Truncated EGF receptors that lack the extracellular ligand-binding domain are constitutively activated, which indicate that the unoccupled extracellular domain acts to prevent kinase activation. Dimerization may also involve direct contact between the helical transmembrane structures of the receptors. Particular mutations within the transmembraneregion cause constitutive dimerization and this, in the case of the ErbB2 receptor(HER-2/neu oncogene), can induce cell transformation.;;3.3 Downstream effectors and pathway;Overview of ERK activation through EGFR;Interaction of Ras and Sos;Activation of Ras ;Interaction of Ras and Raf;Activation of C-Raf;Raf Gene;MEK (MAP kinase –ERK kinase);;Activation of ERK;MNK1, MAP-kinase interacting kinase, is phosphorylated and activated by ERK2. It binds the eukaryotic initiation factor eIF-4E and eIF-4G. MNK1 phosphorylates eIF-4E and this facilitates the association of eIF-3, an essential protein for the assembly of the ribosomal complex;Activated ERKK2 enters the nucleus and phosphorylates transcription factors. In the case of Elk-1 this leads to dimerization with SRF whereas in the case of c-Fos this results in a prolonged half-life and thus more effective induction of transcription. With respect to the cell division cycle, expression of cyclinD is one of the consequences of the action of ERK2. ;Terminati