BIOL 467 Lecture Notes - Lecture 6: Grb2, Sos1, Prostate Cancer
Document Summary
Grb2 monomer-dimer equilibrium determines normal versus oncogenic function (ahmed et al. , 2015) Hypothesis: the dimeric state of grb2 is functionally distinct from monomeric state. Only monomeric grb2 carries out signal transduction. Grb2 functions in the mapk pathway for cell cycle entry. Mitogen (e. g. egf) binds to egrf, which phosphorylates y residues and recruits proteins. Recruits shc, which recruits grb2 or grb2 directly. Grb2 binds to sos, and initiates ras signaling to the mapk pathway at the membrane. Grb2 homodimer showing positions of y160 in pocket at dimer interface. Homodimer with a (green surface) and b (blue, purple ribbon)made mutants y160e and n188, 214d. Flim was used to measure lifetime fret. Left-shift shows a shortening in lifetime indicative of biding this only occurs with grb2 wt (cfp and rfp) vs grb2 y160e or n188 214d cfp and rfp), or controls. See left shift vs in presence of fgfr2.
