浙师大《细胞生物学》chapter11.pptVIP

Activation of RTKs transmit a hormone signal to Ras. 1. Ligand Binding Leads to Autophosphorylation of RTKs 2. Ras Belongs to the GTPase Superfamily of Intracellular Switch Proteins Ras is a GTP-binding switch protein that, like the G a subunits in different G proteins, alternates between an active on state with a bound GTP and an inactive off state with a bound GDP. Ras activation is accelerated by a protein called guanine nucleotide exchange factor (GEF), which binds to the Ras · GDP complex. 3. An Adapter Protein and GEF Link Most Activated RTKs to Ras Activation of Ras following binding of a hormone (e.g., EGF) to an RTK. The adapter protein GRB2 binds to a specific phosphotyrosine on the activated RTK and to Sos, which in turn interacts with the inactive Ras · GDP. The guanine nucleotide exchange factor (GEF) activity of Sos then promotes formation of the active Ras · GTP. The phosphate group of phosphotyrosine (phosphorylated tyrosine) can form several hydrogen bonds with the SH2 (Src homology 2) domain of some proteins involved in the signaling via tyrosine kinases.?? Receptor Tyrosine Kinases Domain structure of some SH2-containing proteins. ???????????????????????????????????????????????????????????????????????????????????????????? The epidermal growth factor (EGF) peptide induces cellular proliferation through the EGF receptor, which has a tyrosine kinase cytoplasmic domain, a single transmembrane domain and an extracellular domain involved in EGF binding and receptor dimerization. Inhibitors of the EGF receptor are being pursued as potential cancer therapies and EGF may stimulate wound healing. Mutation of the EGF receptor has been associated with cancer in humans. The proliferative effects of EGF are signaled through several pathways. Binding of EGF results in EGF receptor dimerization, autophosphorylation of the receptor, and tyrosine phosphorylation of other proteins. The EGF receptor activates ras and the MAP kinase pathway, ultimately c