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Gene Review

Sos  -  Son of sevenless

Drosophila melanogaster

Synonyms: 2.3, 34Ea, BG:DS00941.4, CG7793, Dmel\CG7793, ...
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Disease relevance of Sos

  • To examine whether these sites are substrates for MAP kinases, the cDNA encoding Drosophila Sos (dSos) was tagged with sequences encoding the major antigenic epitope of the influenza virus hemagglutinin (HA) to create a dSosHA fusion construct. dSosHA was transiently expressed in COS-1 cells and immunoprecipitated with anti-HA antibodies [1].
  • In a previous paper, we reported that the reactivity level, which regulates the frequency of transposition of I factor, a LINE element-like retrotransposon, is enhanced by the same agents that induce the SOS response in Escherichia coli [2].
  • In Sf9 cells expressing the TRPL gene along with histamine H1 receptors after infection with baculoviruses containing the corresponding complementary DNA, histamine-induced TRPL currents were inhibited by intracellular Ca2+ with an IC50 of 2.3 microM [3].
  • Medulloblastoma occurred in 4 patients at a mean age of 2.3 years [4].

High impact information on Sos

  • A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos [5].
  • These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation [5].
  • An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro [6].
  • Mutations in Sos also interact with the Ellipse allele of the Drosophila EGF receptor [7].
  • We have isolated a dominant mutation in a gene called Son of sevenless (Sos) that is an allele-specific suppressor of the sevenless phenotype [7].

Biological context of Sos

  • Homozygous loss of Son-of-Sevenless (Sos) also enhances the ctDrac phenotype and causes errors in embryos expressing either dnRho or dnDrac [8].
  • In contrast, a Sos fragment lacking the Drk binding sites was functional and its activity was dependent on the presence of the Sevenless receptor [9].
  • Sos proteins contain numerous sequences in their carboxyl-terminal regions which correspond to consensus sites for MAP kinase phosphorylation [1].
  • The SH3 domains bind to Sos, a guanine nucleotide exchange factor for Ras proteins [10].
  • Son of sevenless-1 and -2 (Sos-1 and -2) are guanosine nucleotide exchange factors implicated in the activation of Ras by both the insulin and epidermal growth factor signal transduction pathways [1].

Anatomical context of Sos

  • Furthermore, we have analyzed the maternal-effect phenotype of Son of sevenless (Sos), a positive regulator of Ras1, and showed that embryos derived from germ cells lacking Sos+ activity exhibit a terminal-class phenotype [11].
  • Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos) [12].
  • Ectopic expression of Drosophila Sos stimulates morphological transformation of rodent fibroblasts [13].
  • As revealed by RNA blot-hybridization analysis, two mRNA species of 2.3 and 3.2 kb are detected in the central nervous system of Lymnaea [14].
  • Activation of p21ras by receptor tyrosine kinases is thought to result from recruitment of guanine nucleotide exchange factors such as Son-of-sevenless (Sos) to plasma membrane receptor substrates via adaptor proteins such as Grb2 [15].

Associations of Sos with chemical compounds

  • This probably stimulates p21ras activity through the mammalian homologue of the Drosophila guanine-nucleotide-exchange factor Sos (reviewed in ref. 11) [16].
  • The effect of binding a proline-rich peptide derived from the protein Sos, a biological target of the drkN SH3 domain, on this equilibrium has been investigated [17].
  • Surprisingly, the COOH-terminal, adaptor binding domain of dSos was not sufficient to confer p21ras exchange activity to the Sos catalytic domain in these cells in the absence of the NH2-terminal domain [15].
  • Circular dichroism spectroscopy, used to monitor thermal denaturations of a heterodimerizing leucine zipper system containing either valine (V) or asparagine (N) in the 'a' position, indicates that the V-N interaction is 2.3 kcal/mole less stable than an N-N interaction and 5.3 kcal/mole less stable than a V-V interaction [18].
  • First, the association rate constant k1 and dissociation rate constant k-1 in the cyclic AMP-regulatory subunit interaction at 0 degrees C were estimated to be 2.3 X 10(6)M-1s-1 and 1.1 X 10(-3)s-1, respectively [19].

Other interactions of Sos

  • Additionally, loss-of-function mutations in Star act as suppressors of R7 development in a sensitized genetic background involving the Son of sevenless (Sos) locus, and overexpression of Star enhances R7 development in this genetic background [20].
  • These genes, which include Sos and Myd88, represent putative targets for miRNA regulation [21].
  • The Son of sevenless (Sos) protein functions as a guanine nucleotide transfer factor for Ras and interacts with the receptor tyrosine kinase Sevenless through the protein Drk, a homolog of mammalian Grb2 [9].
  • Genetic fusion of 16 and 14 amino acid segments of c-Cbl and Sos, respectively, to bacterial alkaline phosphatase confirmed that these segments were potential ligand sites for the C-terminal SH3 domain of CAP [22].

Analytical, diagnostic and therapeutic context of Sos

  • Finally, immunoblotting shows that CD28 also associates with the gene product of the human homolog of the Drosophila Son of sevenless gene (SOS), a GRB-2-complexed guanine nucleotide exchange factor responsible for converting p21ras to a GTP-bound active state [23].
  • Northern blot hybridization with a Bombyx cad probe revealed the presence of single maternal transcript of 2.3 kb [24].
  • Northern blot analysis of RNA isolated from human cells and mouse tissues shows that a single Plk1 mRNA of 2.3 kb is highly expressed in tissues with a high mitotic index, consistent with a possible function of Plk1 in cell proliferation [25].
  • Sequence analysis revealed that all five clones belong to a single family of repetitive DNA elements, which we have named Bm1, and whose reiteration frequency is approximately 2.3 X 10(4) copies per haploid genome [26].
  • Southern blotting studies detected a 2.3 kb DNA deletion within this region in the mutant [27].


  1. Phosphorylation of the Ras nucleotide exchange factor son of sevenless by mitogen-activated protein kinase. Cherniack, A.D., Klarlund, J.K., Czech, M.P. J. Biol. Chem. (1994) [Pubmed]
  2. Evidence for an inducible repair-recombination system in the female germ line of Drosophila melanogaster. II. Differential sensitivity to gamma rays. Laurençon, A., Bregliano, J.C. Genetics (1995) [Pubmed]
  3. Regulation of heterologously expressed transient receptor potential-like channels by calcium ions. Obukhov, A.G., Schultz, G., Lückhoff, A. Neuroscience (1998) [Pubmed]
  4. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Kimonis, V.E., Goldstein, A.M., Pastakia, B., Yang, M.L., Kase, R., DiGiovanna, J.J., Bale, A.E., Bale, S.J. Am. J. Med. Genet. (1997) [Pubmed]
  5. A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Olivier, J.P., Raabe, T., Henkemeyer, M., Dickson, B., Mbamalu, G., Margolis, B., Schlessinger, J., Hafen, E., Pawson, T. Cell (1993) [Pubmed]
  6. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Simon, M.A., Dodson, G.S., Rubin, G.M. Cell (1993) [Pubmed]
  7. Genetic dissection of a neurodevelopmental pathway: Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases. Rogge, R.D., Karlovich, C.A., Banerjee, U. Cell (1991) [Pubmed]
  8. Regulation of rho family GTPases is required to prevent axons from crossing the midline. Fritz, J.L., VanBerkum, M.F. Dev. Biol. (2002) [Pubmed]
  9. In vivo functional analysis of the Ras exchange factor son of sevenless. Karlovich, C.A., Bonfini, L., McCollam, L., Rogge, R.D., Daga, A., Czech, M.P., Banerjee, U. Science (1995) [Pubmed]
  10. The GRB2/Sem-5 adaptor protein. Downward, J. FEBS Lett. (1994) [Pubmed]
  11. Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila. Lu, X., Chou, T.B., Williams, N.G., Roberts, T., Perrimon, N. Genes Dev. (1993) [Pubmed]
  12. Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes. Baltensperger, K., Kozma, L.M., Cherniack, A.D., Klarlund, J.K., Chawla, A., Banerjee, U., Czech, M.P. Science (1993) [Pubmed]
  13. Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Egan, S.E., Giddings, B.W., Brooks, M.W., Buday, L., Sizeland, A.M., Weinberg, R.A. Nature (1993) [Pubmed]
  14. Serotonin receptor cDNA cloned from Lymnaea stagnalis. Sugamori, K.S., Sunahara, R.K., Guan, H.C., Bulloch, A.G., Tensen, C.P., Seeman, P., Niznik, H.B., Van Tol, H.H. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  15. Functional roles for the pleckstrin and Dbl homology regions in the Ras exchange factor Son-of-sevenless. McCollam, L., Bonfini, L., Karlovich, C.A., Conway, B.R., Kozma, L.M., Banerjee, U., Czech, M.P. J. Biol. Chem. (1995) [Pubmed]
  16. Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc. Dilworth, S.M., Brewster, C.E., Jones, M.D., Lanfrancone, L., Pelicci, G., Pelicci, P.G. Nature (1994) [Pubmed]
  17. NMR studies of unfolded states of an SH3 domain in aqueous solution and denaturing conditions. Zhang, O., Forman-Kay, J.D. Biochemistry (1997) [Pubmed]
  18. B-ZIP proteins encoded by the Drosophila genome: evaluation of potential dimerization partners. Fassler, J., Landsman, D., Acharya, A., Moll, J.R., Bonovich, M., Vinson, C. Genome Res. (2002) [Pubmed]
  19. A kinetic study of cyclic adenosine 3':5'-monophosphate binding and mode of activation of protein kinase from Drosophila melanogaster embryos. Tsuzuki, J., Kiger, J.A. Biochemistry (1978) [Pubmed]
  20. Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila. Kolodkin, A.L., Pickup, A.T., Lin, D.M., Goodman, C.S., Banerjee, U. Development (1994) [Pubmed]
  21. Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. Boutla, A., Delidakis, C., Tabler, M. Nucleic Acids Res. (2003) [Pubmed]
  22. Molecular recognition properties of the C-terminal Sh3 domain of the Cbl associated protein, Cap. Kurakin, A., Hoffman, N.G., Kay, B.K. J. Pept. Res. (1998) [Pubmed]
  23. T cell antigen CD28 binds to the GRB-2/SOS complex, regulators of p21ras. Schneider, H., Cai, Y.C., Prasad, K.V., Shoelson, S.E., Rudd, C.E. Eur. J. Immunol. (1995) [Pubmed]
  24. A maternal homeobox gene, Bombyx caudal, forms both mRNA and protein concentration gradients spanning anteroposterior axis during gastrulation. Xu, X., Xu, P.X., Suzuki, Y. Development (1994) [Pubmed]
  25. Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5. Golsteyn, R.M., Schultz, S.J., Bartek, J., Ziemiecki, A., Ried, T., Nigg, E.A. J. Cell. Sci. (1994) [Pubmed]
  26. A highly reiterated family of transcribed oligo(A)-terminated, interspersed DNA elements in the genome of Bombyx mori. Adams, D.S., Eickbush, T.H., Herrera, R.J., Lizardi, P.M. J. Mol. Biol. (1986) [Pubmed]
  27. A DNA deletion associated with multiple impaired transcripts in the visual mutant TRP. Lu, M., Wong, F. Invest. Ophthalmol. Vis. Sci. (1987) [Pubmed]
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