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Gene Review

sev  -  sevenless

Drosophila melanogaster

Synonyms: 7LES, 7less, CG18085, CT3980, DROSEV, ...
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High impact information on sev


Biological context of sev

  • DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila [1].
  • The selD(ptuf) mutation dominantly suppresses the phenotypes in the eye and the wing caused by hyperactivation of the Ras/MAPK cassette and the activated forms of the Drosophila EGF receptor (DER) and Sevenless (Sev) receptor tyrosine kinases (RTKs), which signal in the eye and wing, respectively [5].
  • 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 [6].
  • A single amino acid substitution in the ATP-binding site of the putative kinase domain results in the synthesis of an inactive sev protein unable to determine cell fate [7].
  • We have determined the nucleotide sequence and structure of the sevenless transcription unit [8].

Anatomical context of sev


Associations of sev with chemical compounds

  • Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function [12].
  • Our biochemical analysis suggests that DAB binds SEV directly via its PTB domain, becomes tyrosine phosphorylated upon SEV activation, and then serves as an adaptor protein for SH2 domain-containing proteins [13].
  • Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase [14].
  • We surveyed sequence variation in four X-linked genes (runt, sevenless, Sex-lethal, and vermilion) that have been used in a parallel study in the closely related species D. melanogaster [15].
  • (d) Immunostaining of normal and sevenless heads with histamine-specific antisera demonstrates that histamine is present in photoreceptors R1-6 and R8 [16].

Physical interactions of sev


Enzymatic interactions of sev


Other interactions of sev

  • By screening for mutations that suppress signaling via a constitutively activated SEV protein, we have identified a novel gene, daughter of sevenless (dos) [1].
  • Specification of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell [12].
  • A loss-of-function argos mutation enhanced the overproduction of R7 neurons caused by gain-of-function alleles of Son of sevenless and Dsor1 [18].
  • We report here that Ras1 activation may account for all of the signalling action of Sev; an activated Ras1Va112 protein rescues the normal R7 precursor from transformation into a cone cell in sev and boss null mutants and induces the formation of supernumerary R7 cells [19].
  • The sev gene encodes a receptor protein tyrosine kinase (Sev) localized on the R7 surface, activated by a boss-encoded ligand presented by R8 [19].

Analytical, diagnostic and therapeutic context of sev


  1. DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Raabe, T., Riesgo-Escovar, J., Liu, X., Bausenwein, B.S., Deak, P., Maröy, P., Hafen, E. Cell (1996) [Pubmed]
  2. Daughter of sevenless is a substrate of the phosphotyrosine phosphatase Corkscrew and functions during sevenless signaling. Herbst, R., Carroll, P.M., Allard, J.D., Schilling, J., Raabe, T., Simon, M.A. Cell (1996) [Pubmed]
  3. A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways. Brunner, D., Oellers, N., Szabad, J., Biggs, W.H., Zipursky, S.L., Hafen, E. Cell (1994) [Pubmed]
  4. Drosophila Jun mediates Ras-dependent photoreceptor determination. Bohmann, D., Ellis, M.C., Staszewski, L.M., Mlodzik, M. Cell (1994) [Pubmed]
  5. Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster. Morey, M., Serras, F., Baguñà, J., Hafen, E., Corominas, M. Dev. Biol. (2001) [Pubmed]
  6. Recruitment of the protein tyrosine phosphatase CSW by DOS is an essential step during signaling by the sevenless receptor tyrosine kinase. Herbst, R., Zhang, X., Qin, J., Simon, M.A. EMBO J. (1999) [Pubmed]
  7. Control of photoreceptor cell fate by the sevenless protein requires a functional tyrosine kinase domain. Basler, K., Hafen, E. Cell (1988) [Pubmed]
  8. Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster. Bowtell, D.D., Simon, M.A., Rubin, G.M. Genes Dev. (1988) [Pubmed]
  9. Prepattern in the developing Drosophila eye revealed by an activated torso--sevenless chimeric receptor. Dickson, B., Sprenger, F., Hafen, E. Genes Dev. (1992) [Pubmed]
  10. Genetic dissection of endocytic trafficking in Drosophila using a horseradish peroxidase-bride of sevenless chimera: hook is required for normal maturation of multivesicular endosomes. Sunio, A., Metcalf, A.B., Krämer, H. Mol. Biol. Cell (1999) [Pubmed]
  11. The sevenless+ protein is expressed apically in cell membranes of developing Drosophila retina; it is not restricted to cell R7. Banerjee, U., Renfranz, P.J., Hinton, D.R., Rabin, B.A., Benzer, S. Cell (1987) [Pubmed]
  12. Raf functions downstream of Ras1 in the Sevenless signal transduction pathway. Dickson, B., Sprenger, F., Morrison, D., Hafen, E. Nature (1992) [Pubmed]
  13. Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase. Le, N., Simon, M.A. Mol. Cell. Biol. (1998) [Pubmed]
  14. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Simon, M.A., Bowtell, D.D., Dodson, G.S., Laverty, T.R., Rubin, G.M. Cell (1991) [Pubmed]
  15. Contrasted polymorphism patterns in a large sample of populations from the evolutionary genetics model Drosophila simulans. Baudry, E., Derome, N., Huet, M., Veuille, M. Genetics (2006) [Pubmed]
  16. Histamine: a neurotransmitter candidate for Drosophila photoreceptors. Sarthy, P.V. J. Neurochem. (1991) [Pubmed]
  17. Son of sevenless binds to the SH3 domain of src-type tyrosine kinase. Park, C., Choi, Y., Yun, Y. Mol. Cells (1998) [Pubmed]
  18. The Drosophila secreted protein Argos regulates signal transduction in the Ras/MAPK pathway. Sawamoto, K., Okabe, M., Tanimura, T., Mikoshiba, K., Nishida, Y., Okano, H. Dev. Biol. (1996) [Pubmed]
  19. Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation. Fortini, M.E., Simon, M.A., Rubin, G.M. Nature (1992) [Pubmed]
  20. Genetic dissection of signal transduction mediated by the sevenless receptor tyrosine kinase in Drosophila. Hafen, E., Dickson, B., Brunner, T., Raabe, T. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1993) [Pubmed]
  21. Localization of the sevenless protein, a putative receptor for positional information, in the eye imaginal disc of Drosophila. Tomlinson, A., Bowtell, D.D., Hafen, E., Rubin, G.M. Cell (1987) [Pubmed]
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