Biology 2382B Lecture Notes - Lecture 11: Sh3 Domain, Grb2, Signal Transduction
23 Mar 2014
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Document Summary
Tyrosine kinase activity not present in absence of ligand. Rtk phosphorylates itself, and additional tyrosine residues adjacent to the kinase part of the cytosolic domain. Egf binds egfr; activating egf dimer (an rtk) Sh3 domain binds proline of sos (a guanine nucleotide exchange factor; gef) Sos bins to inactive form of ras; promoting dissociation of gdp and gtp binds ras. Active ras binds inactive raf and removes the inhibitory protein;14-3-3. Mapk can now translocate to the nucleus and activate many transcription factors. Oncogenic receptors promote proliferation in absence of ligand. Mutations can cause spontaneous dimerization and constitutive activation of kinases. Over expression of her2 makes the tumor cells sensitive to growth stimulation by low levels of any member of the egf family of growth factors, levels which would not stimulate proliferation of cells with normal her2 levels. Gene amplification= multiple copies of a gene on a single chromosome due to errors in dna replication.
