High impact information on dos

• Mutations of dos were identified in a screen for dominant mutations which enhance the phenotype caused by overexpression of inactive CSW during photoreceptor development [1].
• By screening for mutations that suppress signaling via a constitutively activated SEV protein, we have identified a novel gene, daughter of sevenless (dos) [2].
• The presence of an amino-terminally located pleckstrin homology domain and many potential tyrosine phosphorylation sites suggests that DOS functions as an adaptor protein able to interact with multiple signaling molecules [2].
• Mutant DOS proteins in which either Y801 or Y854 of DOS has been changed to phenylalanine are unable to function during signaling by SEV and other receptor tyrosine kinases [3].
• The pleckstrin homology (PH) domain-containing protein Daughter of Sevenless (DOS) is an essential component of the Sevenless receptor tyrosine kinase (SEV) signaling cascade, which specifies R7 photoreceptor development in the Drosophila eye [3].

Biological context of dos

• Here, we studied the structural requirements for Dos function in receptor tyrosine kinase mediated signaling processes by expressing mutated dos transgenes in the fly [4].
• The presence of two conserved introns confirmed that the dos and gab genes are orthologous, but the Caenorhabditis elegans soc-1 gene had no unambiguously conserved introns with either dos or gab [5].
• We have investigated this possibility by identifying tyrosine residues 801 and 854 of DOS as the phosphorylated binding sites for the CSW SH2 domains [3].
• The Caenorhabditis elegans EGL-15 signaling pathway implicates a DOS-like multisubstrate adaptor protein in fibroblast growth factor signal transduction [6].
• Here, we have conducted equilibrium dos-inhibition experiments, single channel recording, and mutagenesis in vitro to study the mechanism underlying the inhibition of Shaw2K+ channels by a homologous series of n-alkanols (ethanol to 1-hexanol) [7].

Anatomical context of dos

• Confocal microscopy has been used to correlate organization of microtubules, centrosomal proteins and chromosomes in wild-type and dosach (dos) embryos [8].

Physical interactions of dos

• We show that these sites become phosphorylated in response to SEV activation and that phosphorylation of both sites is required to allow CSW to bind DOS [3].

Enzymatic interactions of dos

• Previous results have suggested that DOS becomes tyrosine phosphorylated during SEV signaling and collaborates with the protein tyrosine phosphatase CSW [3].

Other interactions of dos

• These results indicate that a primary role for DOS during signaling by SEV and other receptor tyrosine kinases is to become phosphorylated at Y801 and Y854 and then recruit CSW [3].
• The Gab/dos/Soc-1 proteins form a family of multi-adaptor/scaffolding proteins involved in receptor tyrosine kinase signaling [5].
• The target sequences for Poils au dos activity were mapped to a 14 kb region around scute [9].

References