Individual receptor states can influence signal output. (a) Grb2 and RasGAP (GAP) bind to distinct sites on the PDGF receptor (blue line). For clarity, only one receptor molecule is shown; the actual activated form of the receptor is a dimer. The consequence of Grb2 binding is Ras activation, through the Ras guanine-nucleotide exchange factor Sos. The consequence of GAP binding is Ras inactivation (by stimulating its intrinsic GTPase activity). Thus, these two effectors have opposing effects on Ras activity. (b) Three different possible distributions of GAP and Grb2 on receptors are depicted; in all cases, an average of 0.5 molecule of Grb2 and 0.5 molecule of GAP are bound per receptor. Left, binding of Grb2 and GAP are positively correlated; middle, binding of Grb2 and GAP are independent; right, binding of Grb2 and GAP are negatively correlated. (c) Effects of different distribution of effectors on Ras activity are depicted. Left, where binding of GAP and Grb2 are positively correlated, Ras activity will be relatively low and uniform. Right, where binding of Grb2 and GAP are negatively correlated, areas of high Ras activity and low Ras activity will be interspersed.
Mayer et al. Journal of Biology 2009 8:81 doi:10.1186/jbiol185