Activation of Ras proteins underlies functional decisions in diverse cell types. Two molecules, Ras-GRP and SOS (Ras–guanine nucleotide–releasing protein and Son of Sevenless, respectively), catalyze Ras activation in lymphocytes. Binding of active Ras to the allosteric pocket of SOS markedly increases the activity of SOS. Thus, there is a positive feedback loop regulating SOS. Combining in silico and in vitro studies, we demonstrate that “digital” signaling in lymphocytes (cells are “on” or “off”) is predicated on this allosteric regulation of SOS. The SOS feedback loop leads to hysteresis in the dose-response curve, which may enable T cells to exhibit “memory” of past encounters with antigen. Ras activation by Ras-GRP alone is “analog” (a graded increase in activation in response to an increase in the amplitude of the stimulus). We describe how the complementary analog (Ras-GRP) and digital (SOS) pathways act on Ras to efficiently convert analog input to digital output and make predictions regarding the importance of digital signaling in lymphocyte function and development.


  • Education > General

Education Levels:


    biostability,network,NSDL_SetSpec_BEN,signal transduction,slideshow,simulation,oai:nsdl.org:2200/20100927005240017T,Life Science,Education,seminar,NSDL



    Access Privileges:

    Public - Available to anyone

    License Deed:

    Creative Commons Attribution Non-Commercial Share Alike


    This resource has not yet been aligned.
    Curriki Rating
    'NR' - This resource has not been rated
    'NR' - This resource has not been rated

    This resource has not yet been reviewed.

    Not Rated Yet.

    Non-profit Tax ID # 203478467