Daughter of sevenless is a substrate of the phosphotyrosine phosphatase Corkscrew and functions during sevenless signaling

Cell. 1996 Jun 14;85(6):899-909. doi: 10.1016/s0092-8674(00)81273-8.

Abstract

The SH2 domain-containing phosphotyrosine phosphatase Corkscrew (CSW) is an essential component of the signaling pathway initiated by the activation of the sevenless receptor tyrosine kinase (SEV) during Drosophila eye development. We have used genetic and biochemical approaches to identify a substrate for CSW. Expression of a catalytically inactive CSW was used to trap CSW in a complex with a 115 kDa tyrosine-phosphorylated substrate. This substrate was purified and identified as the product of the daughter of sevenless (dos) gene. Mutations of dos were identified in a screen for dominant mutations which enhance the phenotype caused by overexpression of inactive CSW during photoreceptor development. Analysis of dos mutations indicates that DOS is a positive component of the SEV signaling pathway and suggests that DOS dephosphorylation by CSW may be a key event during signaling by SEV.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila / enzymology
  • Drosophila / growth & development
  • Drosophila Proteins*
  • Eye Proteins / biosynthesis
  • Eye Proteins / chemistry
  • Eye Proteins / genetics
  • Eye Proteins / isolation & purification
  • Eye Proteins / metabolism*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Molecular Weight
  • Mutation
  • Phosphorylation
  • Photoreceptor Cells, Invertebrate / growth & development*
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • Substrate Specificity
  • src Homology Domains / physiology

Substances

  • Dos protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Receptor Protein-Tyrosine Kinases
  • sev protein, Drosophila
  • Csw protein, Drosophila
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor