drosophila son of sevenless protein


Summary: A guanine nucleotide exchange factor from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.

Top Publications

  1. Maly I, Wiley H, Lauffenburger D. Self-organization of polarized cell signaling via autocrine circuits: computational model analysis. Biophys J. 2004;86:10-22 pubmed
    ..We additionally offer particular suggestions for critical nodes in the EGFR signaling circuits governing this self-organization capability. ..
  2. Santen R, Song R, Zhang Z, Yue W, Kumar R. Adaptive hypersensitivity to estrogen: mechanism for sequential responses to hormonal therapy in breast cancer. Clin Cancer Res. 2004;10:337S-45S pubmed
  3. Tian W, Boss G, Cohen D. Ras signaling in the inner medullary cell response to urea and NaCl. Am J Physiol Cell Physiol. 2000;278:C372-80 pubmed
    ..In addition, urea treatment induced recruitment of the Ras activator Sos to the plasma membrane. Taken together, these observations suggest a role for Ras signaling in the IMCD cell response to urea stress. ..
  4. Smith S, Hyde M, Pincus M. Comparison of the predicted structures of loops in the ras-SOS protein bound to a single ras-p21 protein with the crystallographically determined structures in SOS bound to two ras-p21 proteins. Protein J. 2005;24:391-8 pubmed
    ..We further find that our computed structures for residues 742-743 and 750-751 are superimposable on the X-ray structure for these residues. ..
  5. Mon N, Hasegawa H, Thant A, Huang P, Tanimura Y, Senga T, et al. A role for focal adhesion kinase signaling in tumor necrosis factor-alpha-dependent matrix metalloproteinase-9 production in a cholangiocarcinoma cell line, CCKS1. Cancer Res. 2006;66:6778-84 pubmed
    ..Taken together, our results suggest the pivotal role of FAK in TNF-alpha-dependent production of MMP-9 and subsequent activation of tumor invasion. ..
  6. Nimnual A, Bar Sagi D. The two hats of SOS. Sci STKE. 2002;2002:pe36 pubmed
    ..Nimnual and Bar-Sagi discuss how these two activities of SOS can be regulated and how SOS may be recruited to different cellular locations through interactions with the adaptor proteins Grb2 and E3b1. ..
  7. Gobert Gosse S, Bourgin C, Liu W, Garbay C, Mouchiroud G. M-CSF stimulated differentiation requires persistent MEK activity and MAPK phosphorylation independent of Grb2-Sos association and phosphatidylinositol 3-kinase activity. Cell Signal. 2005;17:1352-62 pubmed
    ..Therefore, M-CSF differentiation signaling in myeloid progenitor cells is mediated through persistent MEK activity but it is not strictly dependent upon Grb2-Sos interaction or PI 3-kinase activity. ..
  8. Correa Meyer E, Pesce L, Guerrero C, Sznajder J. Cyclic stretch activates ERK1/2 via G proteins and EGFR in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2002;282:L883-91 pubmed
    ..Accordingly, in primary AEC, cyclic stretch activates ERK1/2 via G proteins and EGFR, in Na(+) and Ca(2+) influxes and Grb2-SOS-, Ras-, and Raf-1-independent pathways. ..
  9. Tian X, Feig L. Basis for signaling specificity difference between Sos and Ras-GRF guanine nucleotide exchange factors. J Biol Chem. 2001;276:47248-56 pubmed
    ..Although previous studies have shown that helix B of Sos1 and helix 3 of Ha-Ras are involved in promoting nucleotide exchange on Ras proteins, this study highlights the importance of these regions in establishing signaling specificity. ..

More Information


  1. Lee M, Pardoux C, Hall M, Lee P, Warburton D, Qing J, et al. TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007;26:3957-67 pubmed
    ..Thus, TbetaRI, like the TGF-beta type II receptor, is a dual-specificity kinase. Recruitment of tyrosine kinase signalling pathways may account for aspects of TGF-beta biology that are independent of Smad signalling. ..
  2. Fritz J, VanBerkum M. Calmodulin and son of sevenless dependent signaling pathways regulate midline crossing of axons in the Drosophila CNS. Development. 2000;127:1991-2000 pubmed
    ..These data suggest that Calmodulin and Son of sevenless signaling pathways function to interpret midline repulsive cues which prevent axons crossing the midline. ..
  3. Karna E, Trojan S, Pałka J. The mechanism of butyrate-induced collagen biosynthesis in cultured fibroblasts. Acta Pol Pharm. 2009;66:229-33 pubmed
    ..The data suggests that butyrate-dependent stimulation of collagen biosynthesis in cultured human skin fibroblasts undergoes through IGF-IR signaling. ..
  4. Suzuki T, Mitake S, Murata S. Presence of up-stream and downstream components of a mitogen-activated protein kinase pathway in the PSD of the rat forebrain. Brain Res. 1999;840:36-44 pubmed
  5. Karna E, Trojan S, Pałka J. The mechanism of butyrate-induced collagen biosynthesis in cultured fibroblasts. Acta Pol Pharm. 2009;66:129-34 pubmed
    ..The data suggest that butyrate-dependent stimulation of collagen biosynthesis in cultured human skin fibroblasts undergoes through IGF-IR signaling. ..
  6. Yang L, Bashaw G. Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline. Neuron. 2006;52:595-607 pubmed
    ..These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion. ..
  7. Di Fulvio M, Lehman N, Lin X, Lopez I, Gomez Cambronero J. The elucidation of novel SH2 binding sites on PLD2. Oncogene. 2006;25:3032-40 pubmed
    ..When this is released, Y(169) mediates cellular proliferation through the Ras/MAPK pathway. ..
  8. Miltyk W, Karna E, Palka J. Prolidase-independent mechanism of camptothecin-induced inhibition of collagen biosynthesis in cultured human skin fibroblasts. J Biochem. 2007;141:287-92 pubmed
    ..The data suggest that CPT induces inhibition of collagen biosynthesis in cultured human skin fibroblasts by stimulation of NF-kappaB signalling. ..
  9. Itoh R, Kiyokawa E, Aoki K, Nishioka T, Akiyama T, Matsuda M. Phosphorylation and activation of the Rac1 and Cdc42 GEF Asef in A431 cells stimulated by EGF. J Cell Sci. 2008;121:2635-42 pubmed publisher
    ..This observation strongly argues for the positive role of Tyr94 phosphorylation in EGF-induced Asef activation following the activation of Rac1. ..
  10. Settle M, Gordon M, Nadella M, Dankort D, Muller W, Jacobs J. Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model. Oncogene. 2003;22:1916-26 pubmed
    ..These data demonstrate the power of Drosophila genetics to unmask the molecules that signal from oncogenic ErbB-2/Neu. ..
  11. Guerrero C, Pesce L, Lecuona E, Ridge K, Sznajder J. Dopamine activates ERKs in alveolar epithelial cells via Ras-PKC-dependent and Grb2/Sos-independent mechanisms. Am J Physiol Lung Cell Mol Physiol. 2002;282:L1099-107 pubmed
    ..Together, the data suggest that DA activated MAPK/ERK via Ras, Raf-1 kinase, and DAG-dependent PKC isoenzymes, but, importantly and contrary to the classical model, this pathway did not involve the Grb2-Sos complex formation. ..
  12. Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, et al. A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor. J Biol Chem. 2001;276:8856-64 pubmed
    ..These results show that, in addition to Shc and Grb2, a PI3K-dependent pathway involving Gab1 and SHP2 is essential for Ras activation under EGF stimulation. ..
  13. Silver S, Chen F, Doyon L, Zink A, Rebay I. New class of Son-of-sevenless (Sos) alleles highlights the complexities of Sos function. Genesis. 2004;39:263-72 pubmed
    ..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. ..
  14. Koizumi F, Shimoyama T, Taguchi F, Saijo N, Nishio K. Establishment of a human non-small cell lung cancer cell line resistant to gefitinib. Int J Cancer. 2005;116:36-44 pubmed
    ..These phenotypes including EGFR-SOS complex and heterodimer formation of HER family members are potential biomarkers for predicting resistance to gefitinib. ..
  15. Farassati F, Yang A, Lee P. Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1. Nat Cell Biol. 2001;3:745-50 pubmed
  16. Zhou J, Hsieh J. The inhibitory role of DOC-2/DAB2 in growth factor receptor-mediated signal cascade. DOC-2/DAB2-mediated inhibition of ERK phosphorylation via binding to Grb2. J Biol Chem. 2001;276:27793-8 pubmed
    ..This study further illustrates that DOC-2/DAB2 has multiple effects on the RAS-mediated signal cascades active in cancer cells. ..
  17. Quilliam L. New insights into the mechanisms of SOS activation. Sci STKE. 2007;2007:pe67 pubmed
    ..These studies not only enable us to better appreciate the complexity of the regulation of GEFs but also prompt us to reevaluate our current understanding of pathways that lead to Ras activation. ..
  18. Hsouna A, VanBerkum M. Abelson tyrosine kinase and Calmodulin interact synergistically to transduce midline guidance cues in the Drosophila embryonic CNS. Int J Dev Neurosci. 2008;26:345-54 pubmed publisher
  19. Aramini J, Sharma S, Huang Y, Swapna G, Ho C, Shetty K, et al. Solution NMR structure of the SOS response protein YnzC from Bacillus subtilis. Proteins. 2008;72:526-30 pubmed publisher
  20. Brooks S, Li X, Volanakis E, Carter R. Systematic analysis of the role of CD19 cytoplasmic tyrosines in enhancement of activation in Daudi human B cells: clustering of phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines. J Immunol. 2000;164:3123-31 pubmed
    ..CD19 Y391 was also both necessary and sufficient for binding phospholipase C-gamma2. Thus, different tyrosines along the CD19 cytoplasmic domain provide scaffolding for the formation of complexes of different signaling molecules. ..
  21. Li S, Couvillon A, Brasher B, Van Etten R. Tyrosine phosphorylation of Grb2 by Bcr/Abl and epidermal growth factor receptor: a novel regulatory mechanism for tyrosine kinase signaling. EMBO J. 2001;20:6793-804 pubmed
    ..These results suggest that tyrosine phosphorylation of Grb2 is a novel mechanism of down-regulation of tyrosine kinase signaling. ..
  22. Hu Y, Szente B, Kiely J, Gimbrone M. Molecular events in transmembrane signaling via E-selectin. SHP2 association, adaptor protein complex formation and ERK1/2 activation. J Biol Chem. 2001;276:48549-53 pubmed
  23. Watanabe T, Shinohara N, Moriya K, Sazawa A, Kobayashi Y, Ogiso Y, et al. Significance of the Grb2 and son of sevenless (Sos) proteins in human bladder cancer cell lines. IUBMB Life. 2000;49:317-20 pubmed
    ..These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer. ..
  24. Cousin S, Hugl S, Myers M, White M, Reifel Miller A, Rhodes C. Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediate. Biochem J. 1999;344 Pt 3:649-58 pubmed
    ..The additive effect of rGH and IGF-1 on glucose-dependent beta-cell proliferation is therefore reflective of rGH and IGF-1 activating distinctly different mitogenic signalling pathways in beta-cells with minimal crosstalk between them. ..
  25. Kimura A, Ohmichi M, Kurachi H, Ikegami H, Hayakawa J, Tasaka K, et al. Role of mitogen-activated protein kinase/extracellular signal-regulated kinase cascade in gonadotropin-releasing hormone-induced growth inhibition of a human ovarian cancer cell line. Cancer Res. 1999;59:5133-42 pubmed