Disease relevance of TYRO3

• Partial cDNAs of the human TYRO3 gene, encoding a putative receptor tyrosine kinase, and its processed pseudogene (TYRO3P) were cloned from human teratocarcinoma cell, bone marrow and melanocyte cDNA libraries [1].
• Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine endometrial cancers [2].
• The aim is to study for the presence of Gas6 and its receptor Axl and Sky related to specific growth in the ovarian cancers, and to evaluate their plausible growth potential and mechanism [3].
• Clinical implications of coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine leiomyoma [4].
• Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis [5].

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

• The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25 [1].
• TYRO3 and TYRO3P were both assigned to human chromosome 15q14-q25 by analysis of DNAs from somatic cell hybrids [1].
• These results suggest that the Src family kinase may play an important role in signal transduction of the Sky receptor [13].
• Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer [14].
• Analysis of cDNA clones isolated from several tissues shows 2 isoforms of the Etk2/tyro3 gene product that result from usage of alternative exons near the 5' end of the gene [15].

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

• The human DTK gene has been mapped by fluorescent in situ hybridization to chromosome 15q15, and a DTK-related gene identified at chromosome 15q24 [16].
• The apparent relative association and dissociation rate constants of Gas6 for soluble Axl, Rse/Tyro3 and Mer were compared using surface plasmon resonance [22].
• METHODS: In ovarian cancers of 90 cases, the histoscores and mRNA levels of Gas6, Axl and Sky were determined by immunohistochemistry and competitive reverse transcription-polymerase chain reaction-Southern blot analysis using the recombinant RNA, respectively [3].
• In uterine endometrial cancers, the mRNA levels and histoscores of Gas6, Axl and Sky were determined by competitive RT-PCR using recombinant RNA and immunohistochemical studies, respectively [2].
• Molecular cloning, expression and partial characterization of Xksy, Xenopus member of the Sky family of receptor tyrosine kinases [27].

References