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New class of Son‐of‐sevenless ( Sos ) alleles highlights the complexities of Sos function
Author(s) -
Silver Serena J.,
Chen Fangli,
Doyon Laura,
Zink Andrina Williams,
Rebay Ilaria
Publication year - 2004
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20054
Subject(s) - guanine nucleotide exchange factor , allele , genetics , biology , gtpase , signal transduction , complementation , locus (genetics) , small gtpase , microbiology and biotechnology , phenotype , gene
The guanine nucleotide exchange factor (GEF) Son‐of‐sevenless ( Sos ) encodes a complex multidomain protein best known for its role in activating the small GTPase RAS in response to receptor tyrosine kinase (RTK) stimulation. Much less well understood is SOS's role in modulating RAC activity via a separate GEF domain. In the course of a genetic modifier screen designed to investigate the complexities of RTK/RAS signal transduction, a complementation group of 11 alleles was isolated and mapped to the Sos locus. Molecular characterization of these alleles indicates that they specifically affect individual domains of the protein. One of these alleles, Sos M98 , which contains a single amino acid substitution in the RacGEF motif, functions as a dominant negative in vivo to downregulate RTK signaling. These alleles provide new tools for future investigations of SOS‐mediated activation of both RAS and RAC and how these dual roles are coordinated and coregulated during development. genesis 39:263–272, 2004. © 2004 Wiley‐Liss, Inc.