New class of Son-of-sevenless (Sos) alleles highlights the complexities of Sos function.
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, SosM98, 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.
Silver
Serena J
SJ
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Chen
Fangli
F
Doyon
Laura
L
Zink
Andrina Williams
AW
Rebay
Ilaria
I
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D017931:DNA Primers; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics*; D005123:Eye / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*; D020839:Son of Sevenless Protein, Drosophila / Q000235:genetics*; D014921:Wings, Animal / Q000033:anatomy & histology / Q000378:metabolism
D017931:DNA Primers; D020839:Son of Sevenless Protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases