Abstract:
:The classical model for the activation of the nucleotide exchange factor Son of sevenless (SOS) involves its recruitment to the membrane, where it engages Ras. The recent discovery that Ras*GTP is an allosteric activator of SOS indicated that the regulation of SOS is more complex than originally envisaged. We now present crystallographic and biochemical analyses of a construct of SOS that contains the Dbl homology-pleckstrin homology (DH-PH) and catalytic domains and show that the DH-PH unit blocks the allosteric binding site for Ras and suppresses the activity of SOS. SOS is dependent on Ras binding to the allosteric site for both a lower level of activity, which is a result of Ras*GDP binding, and maximal activity, which requires Ras*GTP. The action of the DH-PH unit gates a reciprocal interaction between Ras and SOS, in which Ras converts SOS from low to high activity forms as Ras*GDP is converted to Ras*GTP by SOS.
journal_name
Celljournal_title
Cellauthors
Sondermann H,Soisson SM,Boykevisch S,Yang SS,Bar-Sagi D,Kuriyan Jdoi
10.1016/j.cell.2004.10.005subject
Has Abstractpub_date
2004-10-29 00:00:00pages
393-405issue
3eissn
0092-8674issn
1097-4172pii
S0092867404009511journal_volume
119pub_type
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