BIOM20001 Lecture Notes - Lecture 39: Guanine Nucleotide Exchange Factor, Sh3 Domain, Sh2 Domain
Document Summary
Activated receptor tyrosine kinase (rtk) binds sh2 domain of grb-2. Grb-2 binds via sh3 domain to guanine nucleotide exchange factors (ras gefs) eg sos. It exchanges gdp for gtp on the target ras protein, activating it. Superfamily of monomeric gtpases (ran works in nucleus, rab works for budding vesicles, ras is for signalling) These gtpases function as switches by being in an active or inactive state (has gdp bound) Activated by guanine exchange factors - gefs (eg. Rtk and ras are active only for very short periods. Allows cells to respond quickly and then be turned off quickly. Normally the gtpases (like ras) has a poor ability to hydrolyse gtp. Gtpase with activating proteins (gaps) increases ability to hydrolyse gtp. Ras is oncogenic: hyperactive ras mutants are resistant to inactivation by gap cancer. Therefore need a signalling pathway to rapidly propagate these signals proliferation. Gaps (gtpase activating proteins) switch ras off and differentiation.
