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Gene Review

Tie  -  Tie-like receptor tyrosine kinase

Drosophila melanogaster

Synonyms: CG7525, DPR1, Dmel\CG7525, RTK, tie
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Disease relevance of Tie


High impact information on Tie


Biological context of Tie


Anatomical context of Tie

  • Function of the Drosophila POU domain transcription factor drifter as an upstream regulator of breathless receptor tyrosine kinase expression in developing trachea [14].
  • Control of photoreceptor cell fate by the sevenless protein requires a functional tyrosine kinase domain [15].
  • In vertebrates, however, proximodistal patterning is regulated by receptor tyrosine kinase (RTK) activity from a source of ligands, fibroblast growth factors (FGFs), at the tip of the limb bud [16].
  • We have isolated a RTK that is specifically expressed in electric organ and skeletal muscle [17].
  • Because several other inductive events in development are mediated by receptor tyrosine kinases (RTKs), and because phosphotyrosine staining within muscle fibers is concentrated at synaptic sites, one possibility is that synapse-inducing signals are transduced by a RTK within the muscle fiber [17].

Associations of Tie with chemical compounds


Physical interactions of Tie

  • The INR proreceptor (M(r) 280 kDa) is processed proteolytically to generate an insulin-binding alpha subunit (M(r) 120 kDa) and a beta subunit (M(r) 170 kDa) with protein tyrosine kinase domain [22].
  • Son of sevenless binds to the SH3 domain of src-type tyrosine kinase [23].

Enzymatic interactions of Tie

  • Torso contains a split tyrosine kinase domain and belongs to the type III subgroup of the RTK superfamily that also includes the platelet-derived growth factor receptors, stem cell or steel factor receptor c-Kit proto-oncoprotein, colony-stimulating factor-1 receptor, and vascular endothelial growth factor receptor [24].

Regulatory relationships of Tie


Other interactions of Tie

  • This work provides the first genetic evidence that both Src42A and sag are modulators of RTK signaling [30].
  • Sprouty is a general inhibitor of receptor tyrosine kinase signaling [31].
  • Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system [32].
  • Dof is needed in these cells for activation of the MAPK cascade via FGF signaling, but not for activation via other RTK ligands [33].
  • In support of this hypothesis, we demonstrate that SHP-2, a vertebrate PTPase similar to Csw and previously implicated in RTK signaling, encodes the functional vertebrate homologue of Csw [34].

Analytical, diagnostic and therapeutic context of Tie


  1. DNA sequence, structure, and tyrosine kinase activity of the Drosophila melanogaster Abelson proto-oncogene homolog. Henkemeyer, M.J., Bennett, R.L., Gertler, F.B., Hoffmann, F.M. Mol. Cell. Biol. (1988) [Pubmed]
  2. ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Vidal, M., Wells, S., Ryan, A., Cagan, R. Cancer Res. (2005) [Pubmed]
  3. A Drosophila model of multiple endocrine neoplasia type 2. Read, R.D., Goodfellow, P.J., Mardis, E.R., Novak, N., Armstrong, J.R., Cagan, R.L. Genetics (2005) [Pubmed]
  4. Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo. Lorén, C.E., Scully, A., Grabbe, C., Edeen, P.T., Thomas, J., McKeown, M., Hunter, T., Palmer, R.H. Genes Cells (2001) [Pubmed]
  5. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Lloyd, T.E., Atkinson, R., Wu, M.N., Zhou, Y., Pennetta, G., Bellen, H.J. Cell (2002) [Pubmed]
  6. CNK, a RAF-binding multidomain protein required for RAS signaling. Therrien, M., Wong, A.M., Rubin, G.M. Cell (1998) [Pubmed]
  7. PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism. Tang, A.H., Neufeld, T.P., Kwan, E., Rubin, G.M. Cell (1997) [Pubmed]
  8. 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]
  9. Specificity of FGF signaling in cell migration in Drosophila. Dossenbach, C., Röck, S., Affolter, M. Development (2001) [Pubmed]
  10. Alternative splicing generates two distinct transcripts for the Drosophila melanogaster fibroblast growth factor receptor homolog. Ito, M., Matsui, T., Taniguchi, T., Chihara, K. Gene (1994) [Pubmed]
  11. JUN cooperates with the ETS domain protein pointed to induce photoreceptor R7 fate in the Drosophila eye. Treier, M., Bohmann, D., Mlodzik, M. Cell (1995) [Pubmed]
  12. Genetic analysis of a Drosophila neural cell adhesion molecule: interaction of fasciclin I and Abelson tyrosine kinase mutations. Elkins, T., Zinn, K., McAllister, L., Hoffmann, F.M., Goodman, C.S. Cell (1990) [Pubmed]
  13. The Drosophila Abelson proto-oncogene homolog: identification of mutant alleles that have pleiotropic effects late in development. Henkemeyer, M.J., Gertler, F.B., Goodman, W., Hoffmann, F.M. Cell (1987) [Pubmed]
  14. Function of the Drosophila POU domain transcription factor drifter as an upstream regulator of breathless receptor tyrosine kinase expression in developing trachea. Anderson, M.G., Certel, S.J., Certel, K., Lee, T., Montell, D.J., Johnson, W.A. Development (1996) [Pubmed]
  15. Control of photoreceptor cell fate by the sevenless protein requires a functional tyrosine kinase domain. Basler, K., Hafen, E. Cell (1988) [Pubmed]
  16. Distalization of the Drosophila leg by graded EGF-receptor activity. Campbell, G. Nature (2002) [Pubmed]
  17. Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases. Jennings, C.G., Dyer, S.M., Burden, S.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  18. 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]
  19. Input from Ras is required for maximal PI(3)K signalling in Drosophila. Orme, M.H., Alrubaie, S., Bradley, G.L., Walker, C.D., Leevers, S.J. Nat. Cell Biol. (2006) [Pubmed]
  20. Early evolutionary origin of the neurotrophin receptor family. van Kesteren, R.E., Fainzilber, M., Hauser, G., van Minnen, J., Vreugdenhil, E., Smit, A.B., Ibáñez, C.F., Geraerts, W.P., Bulloch, A.G. EMBO J. (1998) [Pubmed]
  21. Characterization of downstream elements in a Raf-1 pathway. Liaw, G.J., Steingrimsson, E., Pignoni, F., Courey, A.J., Lengyel, J.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  22. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. Fernandez, R., Tabarini, D., Azpiazu, N., Frasch, M., Schlessinger, J. EMBO J. (1995) [Pubmed]
  23. Son of sevenless binds to the SH3 domain of src-type tyrosine kinase. Park, C., Choi, Y., Yun, Y. Mol. Cells (1998) [Pubmed]
  24. Functions and mechanisms of receptor tyrosine kinase Torso signaling: lessons from Drosophila embryonic terminal development. Li, W.X. Dev. Dyn. (2005) [Pubmed]
  25. Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila. Lesokhin, A.M., Yu, S.Y., Katz, J., Baker, N.E. Dev. Biol. (1999) [Pubmed]
  26. Response of Djun and Dfos mRNA abundance to signal transduction pathways in cultured cells of Drosophila melanogaster. Xia, X., Goldstein, E.S. Mol. Biol. Rep. (1999) [Pubmed]
  27. Receptor tyrosine kinase signaling regulates different modes of Groucho-dependent control of Dorsal. Häder, T., Wainwright, D., Shandala, T., Saint, R., Taubert, H., Brönner, G., Jäckle, H. Curr. Biol. (2000) [Pubmed]
  28. In vivo functional analysis of the daughter of sevenless protein in receptor tyrosine kinase signaling. Bausenwein, B.S., Schmidt, M., Mielke, B., Raabe, T. Mech. Dev. (2000) [Pubmed]
  29. Coactivation of STAT and Ras is required for germ cell proliferation and invasive migration in Drosophila. Li, J., Xia, F., Li, W.X. Dev. Cell (2003) [Pubmed]
  30. A genetic screen for modifiers of drosophila Src42A identifies mutations in Egfr, rolled and a novel signaling gene. Zhang, Q., Zheng, Q., Lu, X. Genetics (1999) [Pubmed]
  31. Sprouty is a general inhibitor of receptor tyrosine kinase signaling. Reich, A., Sapir, A., Shilo, B. Development (1999) [Pubmed]
  32. Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system. Lee, T., Hacohen, N., Krasnow, M., Montell, D.J. Genes Dev. (1996) [Pubmed]
  33. The Drosophila protein Dof is specifically required for FGF signaling. Vincent, S., Wilson, R., Coelho, C., Affolter, M., Leptin, M. Mol. Cell (1998) [Pubmed]
  34. The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila. Perkins, L.A., Johnson, M.R., Melnick, M.B., Perrimon, N. Dev. Biol. (1996) [Pubmed]
  35. Genetic dissection of signal transduction mediated by the sevenless receptor tyrosine kinase in Drosophila. Hafen, E., Dickson, B., Brunner, D., Raabe, T. Prog. Neurobiol. (1994) [Pubmed]
  36. Characterization and cloning of a 58/53-kDa substrate of the insulin receptor tyrosine kinase. Yeh, T.C., Ogawa, W., Danielsen, A.G., Roth, R.A. J. Biol. Chem. (1996) [Pubmed]
  37. Dissection of signaling pathways and cloning of new signal transducers in tyrosine kinase-induced pathways by genetic selection. Mahlmann, S., McLaughlin, J., Afar, D.E., Mohr, R., Kay, R.J., Witte, O.N. Leukemia (1998) [Pubmed]
  38. Sampling the genomic pool of protein tyrosine kinase genes using the polymerase chain reaction with genomic DNA. Oates, A.C., Wollberg, P., Achen, M.G., Wilks, A.F. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  39. Regulated cationic channel function in Xenopus oocytes expressing Drosophila big brain. Yanochko, G.M., Yool, A.J. J. Neurosci. (2002) [Pubmed]
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