4ff8

Structural highlights

Function

[TYRO3_MOUSE] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.^{[1] [2] [3] [4]}

References

1. ↑ Angelillo-Scherrer A, Burnier L, Flores N, Savi P, DeMol M, Schaeffer P, Herbert JM, Lemke G, Goff SP, Matsushima GK, Earp HS, Vesin C, Hoylaerts MF, Plaisance S, Collen D, Conway EM, Wehrle-Haller B, Carmeliet P. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest. 2005 Feb;115(2):237-46. PMID:15650770 doi:http://dx.doi.org/10.1172/JCI22079
2. ↑ Sun B, Qi N, Shang T, Wu H, Deng T, Han D. Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors. Endocrinology. 2010 Jun;151(6):2886-97. doi: 10.1210/en.2009-1498. Epub 2010 Apr , 2. PMID:20363878 doi:http://dx.doi.org/10.1210/en.2009-1498
3. ↑ Zhong Z, Wang Y, Guo H, Sagare A, Fernandez JA, Bell RD, Barrett TM, Griffin JH, Freeman RS, Zlokovic BV. Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding globulin-like region. J Neurosci. 2010 Nov 17;30(46):15521-34. doi: 10.1523/JNEUROSCI.4437-10.2010. PMID:21084607 doi:http://dx.doi.org/10.1523/JNEUROSCI.4437-10.2010
4. ↑ Guo H, Barrett TM, Zhong Z, Fernandez JA, Griffin JH, Freeman RS, Zlokovic BV. Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway. Mol Neurodegener. 2011 Feb 3;6:13. doi: 10.1186/1750-1326-6-13. PMID:21291561 doi:http://dx.doi.org/10.1186/1750-1326-6-13
5. ↑ Powell NA, Hoffman JK, Ciske FL, Kaufman MD, Kohrt JT, Quin J 3rd, Sheehan DJ, Delaney A, Baxi SM, Catana C, McConnell P, Ohren J, Perrin LA, Edmunds JJ. Highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. Bioorg Med Chem Lett. 2013 Feb 15;23(4):1046-50. doi: 10.1016/j.bmcl.2012.12.013., Epub 2012 Dec 20. PMID:23312472 doi:http://dx.doi.org/10.1016/j.bmcl.2012.12.013