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Gene Review

TYRO3  -  TYRO3 protein tyrosine kinase

Homo sapiens

Synonyms: BYK, Brt, DTK, Dtk, Etk-2, ...
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Disease relevance of TYRO3


Psychiatry related information on TYRO3

  • Parametric data (13 stimulus onset asynchronies) from an experiment with pairs of visual stimuli (626-nm LEDs) confirm that, relative to central signals (3 degrees), peripheral signals (35 degrees) yield slower reaction times, more strongly modulated RSE time-course functions, and flatter TOJ psychometric functions [6].
  • Extracted factors were compared across case and control groups in the whole sample (N=431) and in a sub-sample (N=301) with low self-esteem (RSE <20) [7].
  • However in the low RSE group only self-confidence was found to be decreased in subjects with mood disorders (SC: F=13.8, p<0.01; SD: F=0.05, p=0.9) [7].

High impact information on TYRO3

  • Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3 [8].
  • The frequency of growing LPS-reactive, normal B cells in spleen of 6-8 week old C3H/Tif mice was determined by limiting dilution analysis to be one of three splenic B cells [9].
  • Treatment of NIH3T3 cells expressing a full length of rat Tyro-3, but not NIH3T3 cells, with protein S also resulted in phosphorylation of Akt [10].
  • The authors previously reported cloning and characterization of the receptor tyrosine kinase Tif, also termed Tyro3 [10].
  • The related Axl, Sky and Mer receptor tyrosine kinases (RTKs) are increasingly being implicated in a host of discrete cellular responses including cell survival, proliferation, migration and phagocytosis [11].

Chemical compound and disease context of TYRO3

  • Moreover, in a mouse model of thrombosis, administration of Gas6 or Sky blocking antibodies resulted in a decrease in thrombus weight similar to clopidogrel but, unlike clopidogrel, produced no increase in template bleeding [12].

Biological context of TYRO3


Anatomical context of TYRO3

  • The ETK2/TYRO3 receptor is a tyrosine kinase expressed in embryonic stem cells, brain and testis that has recently been cloned by several groups [15].
  • In fetal tissues, transcripts for DTK were detected in brain, kidney, lung and heart [16].
  • Immunoblot analysis using an antibody raised against a C-terminal peptide of Sky identified a 98-kDa Sky protein in COS cells transfected with sky cDNA (COS/sky cells) [13].
  • In the immunohistochemical study, Gas6, Axl and Sky were found in endometrial glandular cells and stromal cells in all samples analysed [5].
  • There was no significant difference between the histoscores and levels of Sky mRNA in uterine leiomyoma and normal uterine myometrium, although the levels of Gas6 and Axl mRNAs in uterine leiomyoma were significantly higher than in normal uterine myometrium in each case [4].

Associations of TYRO3 with chemical compounds

  • When the lysates of COS/sky cells were immunoprecipitated with anti-Sky antibody and immunoblotted with an anti-phosphotyrosine antibody, a 60-kDa phosphotyrosine-containing protein, in addition to the tyrosine-phosphorylated Sky, was detected [13].
  • Reported treatments for RSE include very high dose PB, continuous infusions of pentobarbital or BZDs (DZP, midazolam), lidocaine, inhalation anesthesia, and propofol [17].
  • RSE embryos can be produced in embryos expressing the 5HT-R by exposure to serotonin, beginning as late as 12 h postfertilization (pf) [18].
  • In vitro, 1% EtOH retracted RSE cell margins, enhanced transendothelial Evans blue-albumin flux and suppressed proliferative index [19].
  • Preferences for GCSE refractory to two AEDs (RSE) varied: 43% would give phenobarbital, 19% would give one of three continuous-infusion (cIV) AEDs (pentobarbital, midazolam, propofol), and 16% would give IV valproic acid [20].

Enzymatic interactions of TYRO3

  • Vitamin K-dependent protein S and the product of growth-arrest-specific gene 6 (Gas6) both possess the ability to phosphorylate members of the Axl/Sky subfamily of receptor tyrosine kinases [21].

Regulatory relationships of TYRO3

  • Gas6 has previously been shown to activate both Axl and Rse/Tyro3, two other receptor tyrosine kinases in the same family as Mer [22].
  • We found that human protein S may indeed activate human Sky but only above physiological plasma concentrations [21].

Other interactions of TYRO3

  • RanBPM was also found to interact in yeast with the Axl homologue, Sky/Tyro3 [23].
  • Using the anti-Src antibody, which is reactive to Src, Fyn and Yes, we obtained evidence for an association between the Src family tyrosine kinase and the tyrosine-phosphorylated Sky receptor [13].
  • Protein S and a structurally similar protein, Gas6, have been found to stimulate members of the Axl/Sky family of receptor tyrosine kinases [24].
  • A cDNA for this receptor, designated developmental tyrosine kinase (DTK), was isolated and encodes a protein with structural similarities to AXL [25].
  • Using quantitative real-time PCR there was over-expression of epidermal growth factor receptor, c-myc, transforming growth factor-alpha, vascular endothelial growth factor and vimentin, and under-expression of TYRO3 protein tyrosine kinase [26].

Analytical, diagnostic and therapeutic context of TYRO3


  1. The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25. Polvi, A., Armstrong, E., Lai, C., Lemke, G., Huebner, K., Spritz, R.A., Guida, L.C., Nicholls, R.D., Alitalo, K. Gene (1993) [Pubmed]
  2. Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine endometrial cancers. Sun, W.S., Fujimoto, J., Tamaya, T. Ann. Oncol. (2003) [Pubmed]
  3. Coexpression of Gas6/Axl in human ovarian cancers. Sun, W., Fujimoto, J., Tamaya, T. Oncology (2004) [Pubmed]
  4. Clinical implications of coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine leiomyoma. Sun, W.S., Fujimoto, J., Tamaya, T. Mol. Hum. Reprod. (2003) [Pubmed]
  5. Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis. Sun, W.S., Misao, R., Iwagaki, S., Fujimoto, J., Tamaya, T. Mol. Hum. Reprod. (2002) [Pubmed]
  6. On the relationship between the redundant signals effect and temporal order judgments: parametric data and a new model. Schwarz, W. Journal of experimental psychology. Human perception and performance. (2006) [Pubmed]
  7. Components of self-esteem in affective patients and non-psychiatric controls. Serretti, A., Olgiati, P., Colombo, C. Journal of affective disorders. (2005) [Pubmed]
  8. Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3. Godowski, P.J., Mark, M.R., Chen, J., Sadick, M.D., Raab, H., Hammonds, R.G. Cell (1995) [Pubmed]
  9. Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte. Andersson, J., Coutinho, A., Lernhardt, W., Melchers, F. Cell (1977) [Pubmed]
  10. Transforming activity of receptor tyrosine kinase tyro3 is mediated, at least in part, by the PI3 kinase-signaling pathway. Lan, Z., Wu, H., Li, W., Wu, S., Lu, L., Xu, M., Dai, W. Blood (2000) [Pubmed]
  11. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Hafizi, S., Dahlbäck, B. Cytokine Growth Factor Rev. (2006) [Pubmed]
  12. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses. Gould, W.R., Baxi, S.M., Schroeder, R., Peng, Y.W., Leadley, R.J., Peterson, J.T., Perrin, L.A. J. Thromb. Haemost. (2005) [Pubmed]
  13. Autophosphorylation activity and association with Src family kinase of Sky receptor tyrosine kinase. Toshima, J., Ohashi, K., Iwashita, S., Mizuno, K. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  14. Structural basis for Gas6-Axl signalling. Sasaki, T., Knyazev, P.G., Clout, N.J., Cheburkin, Y., Göhring, W., Ullrich, A., Timpl, R., Hohenester, E. EMBO J. (2006) [Pubmed]
  15. Identification of alternative exons, including a novel exon, in the tyrosine kinase receptor gene Etk2/tyro3 that explain differences in 5' cDNA sequences. Biesecker, L.G., Giannola, D.M., Emerson, S.G. Oncogene (1995) [Pubmed]
  16. Isolation and characterization of the human DTK receptor tyrosine kinase. Crosier, K.E., Hall, L.R., Lewis, P.M., Morris, C.M., Wood, C.R., Morris, J.C., Crosier, P.S. Growth Factors (1994) [Pubmed]
  17. Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment. Mitchell, W.G. Epilepsia (1996) [Pubmed]
  18. Ligand-dependent stimulation of introduced mammalian brain receptors alters spicule symmetry and other morphogenetic events in sea urchin embryos. Cameron, R.A., Smith, L.C., Britten, R.J., Davidson, E.H. Mech. Dev. (1994) [Pubmed]
  19. Alcohol, hepatic sinusoidal microcirculation, and chronic liver disease. Witte, M.H., Borgs, P., Way, D.L., Ramirez, G., Bernas, M.J., Witte, C.L. Alcohol (1992) [Pubmed]
  20. Treatment of status epilepticus: a survey of neurologists. Claassen, J., Hirsch, L.J., Mayer, S.A. J. Neurol. Sci. (2003) [Pubmed]
  21. The first laminin G-type domain in the SHBG-like region of protein S contains residues essential for activation of the receptor tyrosine kinase sky. Evenäs, P., Dahlbäck, B., García de Frutos, P. Biol. Chem. (2000) [Pubmed]
  22. Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Chen, J., Carey, K., Godowski, P.J. Oncogene (1997) [Pubmed]
  23. The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases. Hafizi, S., Gustafsson, A., Stenhoff, J., Dahlbäck, B. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  24. Stimulation of Sky tyrosine phosphorylation by bovine protein S--domains involved in the receptor-ligand interaction. Nyberg, P., He, X., Härdig, Y., Dahlback, B., García de Frutos, P. Eur. J. Biochem. (1997) [Pubmed]
  25. Identification of a novel receptor tyrosine kinase expressed in acute myeloid leukemic blasts. Crosier, P.S., Hall, L.R., Vitas, M.R., Lewis, P.M., Crosier, K.E. Leuk. Lymphoma (1995) [Pubmed]
  26. Gene expression profiling of renal cell carcinoma: a DNA macroarray analysis. Lovisolo, J.A., Casati, B., Clerici, L., Marafante, E., Bono, A.V., Celato, N., Salvadore, M. BJU Int. (2006) [Pubmed]
  27. Molecular cloning, expression and partial characterization of Xksy, Xenopus member of the Sky family of receptor tyrosine kinases. Kishi, Y.A., Funakoshi, H., Matsumoto, K., Nakamura, T. Gene (2002) [Pubmed]
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