Disease relevance of Tyro3

• Mechanism of stimulation of osteoclastic bone resorption through Gas6/Tyro 3, a receptor tyrosine kinase signaling, in mouse osteoclasts [1].
• The effect of acute carbon monoxide (CO) breathing on blood oxygenation and tumour hypoxia was related to the radiation response of the C3H/Tif mammary carcinoma [2].
• This tumor model was C3H/Tif mammary adenocarcinoma in C3D2F1/Bom mouse strain [3].
• Tissue metal net cages were implanted subcutaneously in BALB/cJ and C3H/Tif mice as an experimental model of Borrelia burgdorferi infection [4].
• Splenic lymphocytes from CBA/J, AKR/A/J, BALB/c/A, C57/BL/6J, C3H/HeJ and C3H/Tif nu/nu mice and B lymphocyte or T lymphocyte preparations derived from CBA/J mouse spleen were cultivated in the presence of either concanavalin A, phytohemagglutinin, Salmonella minnesota R595 lipopolysaccharide or Proteus mirabilis soluble lipoprotein [5].

High impact information on Tyro3

• We have generated and analysed null mutations in the mouse genes encoding three structurally related receptors with tyrosine kinase activity: Tyro 3, Axl, and Mer [6].
• Here we show that the concerted activation of Tyro 3, Axl and Mer in Sertoli cells is critical to the role that these cells play as nurturers of developing germ cells [6].
• Tyro-3 family receptors are essential regulators of mammalian spermatogenesis [6].
• Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family [7].
• Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases [8].

Biological context of Tyro3

• Receptor tyrosine kinase gene Tyro3 maps to mouse chromosome 2, closely linked to Ltk [9].
• An isoform of Dtk is generated by differential splicing of exons from the 5' region of the gene [10].
• Oligodendrocyte cultures established from wild-type and Rse(-/-) mice, but not from Axl(-/-) mice, were also protected from TNFalpha-induced cell death when maintained in rhgas6 [11].
• The results suggest that signals from differentiated germ cells suppress Sky gene expression in Sertoli cells [12].
• Finally, we demonstrate that loss of Mer function is accompanied by a substantial down-regulation in Tyro 3 as well [13].

Anatomical context of Tyro3

• Conversely, two other family members, Tyro3 and Mer, were not detected in mouse sera and conditioned medium. sAxl is constitutively released by murine primary cells such as dendritic and transformed cell lines [14].
• Together with Axl and Rse, the three RTKs are believed to play important functional roles in the male gonads because gene knockout male mice lacking all of these receptors are infertile [15].
• Gas6 mRNA is present in both spinal motor neurons and large neurons of the dorsal root ganglia, and neural injury has been reported to upregulate Rse/Axl in the schwann cell [16].
• The expression of its receptor, Tyro 3, was seen only in mature osteoclasts among bone cells [1].
• Introduction of murine Sky into RatB1a fibroblasts by retrovirus-mediated gene transfer results in morphological transformation, growth in soft agar, and the formation of tumors in nude mice [17].

Associations of Tyro3 with chemical compounds

• To study the synthesis and activation of this putative receptor-type tyrosine kinase, we constructed a version of Rse (termed gD-Rse, where gD represents glycoprotein D) that contains an NH2-terminal epitope tag [18].
• The frequencies of lipopolysaccharide (LPS)-and lipoprotein-reactive precursors for IgG-secreting cells in the spleen of 6--8 wk old C3H/Tif and of C57BL/67 mice were found to be between 1 in 30 and 1 in 40 B cells and, therefore, only one tenth of the frequencies of mitogen-reactive precursors of clones secreting IgM [19].
• Compared with the F1 hybrid strain the parental inbred strains DBA 2 J and C3H/Tif demonstrated a certain resistance to streptozotocin [20].
• The relationship between hydralazine-induced changes in blood pressure and tumor blood flow was investigated in restrained but non-anesthetized CDF1 mice bearing C3H/Tif foot tumors [21].
• The effect of systemic treatment with the anti-inflammatory drug indomethacin on sun-induced skin carcinogenesis was examined in lightly pigmented hairless hr/hr C3H/Tif mice [22].

Analytical, diagnostic and therapeutic context of Tyro3

• NIH3T3 cells were engineered to express gD-Rse, which could be detected at the cell surface by fluorescence-activated cell sorting [18].
• Immunoblot and immunoprecipitation analyses with anti-Tyro 3 antibodies indicate that the 125 kD Tyro 3 protein is abundantly expressed in CNS synaptosomes, and immunohistochemical analysis of cultured hippocampal cells demonstrates that Tyro 3 is a product of neurons [23].
• Immunohistochemistry revealed that Tyro 3 was expressed on the multinucleated osteoclasts which were positive for tartrate-resistant acid phosphatase (TRAP), but not on mononuclear TRAP-positive cells [24].
• We have examined the expression of receptor tyrosine kinase by polymerase chain reaction (PCR) and found that Tyro 3 was frequently identified from primary osteoclasts in PCR cloning [24].
• The numbers of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were significantly reduced 24 h later by the LF treatments compared to the findings for the control group [25].

References