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The role of the PH domain in the signal‐dependent membrane targeting of Sos
Author(s) -
Chen R.H.,
CorbalanGarcia S.,
BarSagi D.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.6.1351
Subject(s) - biology , domain (mathematical analysis) , signal (programming language) , biophysics , microbiology and biotechnology , computational biology , genetics , mathematical analysis , mathematics , computer science , programming language
The pleckstrin homology (PH) domain is a conserved protein module present in diverse signal transducing proteins. To investigate the function of the PH domain of the Ras exchanger Sos, we have generated a recombinant (His) 6 ‐tagged PH domain from human Sos1 (PH‐Sos). Here we show that PH‐Sos binds with high affinity(1.5 μM) to lipid vesicles containing the negatively charged phospholipid phosphatidylinositol 4,5‐bisphosphate (PIP 2 ). When microinjected into serum‐deprived rat embryo fibroblasts or COS cells, PH‐Sos displays a homogenous subcellular distribution. However, PH‐Sos rapidly accumulates in the plasma membrane following serum stimulation and, under these conditions, is localized preferentially to the leading edge of motile cells. Surprisingly, the membrane localization of PH‐Sos is not dependent on its ability to bind PIP 2 . Overexpression of the PH domain of Sos has a pronounced dominant‐negative effect on serum‐induced activation of the Ras signaling pathway. These results suggest that the PH domain of Sos participates in regulating the inducible association of Sos with the membrane, and indicate the presence of specific ligands that interact with this domain to bring about the activation of Ras.