Alternative titles; symbols
HGNC Approved Gene Symbol: LTK
Cytogenetic location: 15q15.1 Genomic coordinates (GRCh38): 15:41,503,637-41,513,827 (from NCBI)
Ben-Neriah and Bauskin (1988) isolated and characterized the complementary DNA for the mouse leukocyte tyrosine kinase locus. They used the insulin receptor-related avian sarcoma oncogene v-ros (165020) as a probe to isolate the cDNA from a mouse pre-B lymphocyte cDNA library. Northern analysis revealed expression of the gene in thymus, spleen, and kidney. Sequence analysis of the gene revealed similarities with several tyrosine kinase receptor genes of the insulin receptor family. The LTK gene, however, is unique in that it encodes a transmembrane protein that lacks an extracellular domain. The authors suggested that LTK may encode a signal transduction subunit for one or more of the hematopoietic receptors.
Toyoshima et al. (1993) cloned a set of cDNAs representing differently spliced human LTK mRNAs. These cDNAs predicted a truncated receptor protein that lacks the tyrosine kinase domain and a soluble receptor protein that has neither a transmembrane nor a tyrosine kinase domain. A cDNA clone containing the complete open reading frame demonstrated that the extracellular domain of the receptor protein is larger than previously predicted. Thus, the LTK gene produces not only the putative receptor tyrosine kinase for an unknown ligand but also multiple protein products that may have different functions.
Krolewski et al. (1990) mapped the TYK1 gene to chromosome 15 by Southern analysis of somatic cell hybrid DNAs. Richard et al. (1994) mapped many loci on chromosome 15, which they subdivided into 5 regions. By PCR, they concluded that the LTK gene is located in their region III: 15q15.1-q21.1.
Liao et al. (1996) found that the mouse Ltk gene is closely linked to the Tyro3 gene (600341), which maps to mouse chromosome 2.
Systemic lupus erythematosus (SLE; 152700), a complex multigenic disease, is characterized by production of autoantibodies and immune complex-type tissue inflammation. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells may initiate and propagate the disease. In SLE-prone New Zealand black (NZB) mice and their F1 cross with New Zealand white (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Li et al. (2004) performed a genomewide scan for susceptibility genes for aberrant activation of B1 cells in F1/NZB backcross mice and identified Ltk as a possible candidate. Sequence and functional analyses of the gene revealed that NZB mice have a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PIK3R1; 171833). SLE patients had the equivalent human LTK polymorphism at a significantly higher frequency compared to healthy controls. Li et al. (2004) suggested that this LTK SNP may cause upregulation of the PI3K pathway and possibly form a genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.
Ben-Neriah, Y., Bauskin, A. R. Leukocytes express a novel gene encoding a putative transmembrane protein-kinase devoid of an extracellular domain. (Letter) Nature 333: 672-676, 1988. [PubMed: 2836739] [Full Text: https://doi.org/10.1038/333672a0]
Krolewski, J. J., Lee, R., Eddy, R., Shows, T. B., Dalla-Favera, R. Identification and chromosomal mapping of new human tyrosine kinase genes. Oncogene 5: 277-282, 1990. [PubMed: 2156206]
Li, N., Nakamura, K., Jiang, Y., Tsurui, H., Matsuoka, S., Abe, M., Ohtsuji, M., Nishimura, H., Kato, K., Kawai, T., Atsumi, T., Koike, T., Shirai, T., Ueno, H., Hirose, S. Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus. Hum. Molec. Genet. 13: 171-179, 2004. [PubMed: 14695357] [Full Text: https://doi.org/10.1093/hmg/ddh020]
Liao, X., Zhou, R., Gilbert, D. J., Copeland, N. G., Jenkins, N. A. Receptor tyrosine kinase gene Tyro3 maps to mouse chromosome 2, closely linked to Ltk. Mammalian Genome 7: 395-396, 1996. [PubMed: 8661736] [Full Text: https://doi.org/10.1007/s003359900116]
Richard, I., Broux, O., Chiannilkulchai, N., Fougerousse, F., Allamand, V., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Lorenzo, F., Sebastiani-Kabatchis, C., Schultz, R. A., Polymeropoulos, M. H., Gyapay, G., Auffray, C., Beckmann, J. S. Regional localization of human chromosome 15 loci. Genomics 23: 619-627, 1994. [PubMed: 7851890] [Full Text: https://doi.org/10.1006/geno.1994.1550]
Toyoshima, H., Kozutsumi, H., Maru, Y., Hagiwara, K., Furuya, A., Mioh, H., Hanai, N., Takaku, F., Yazaki, Y., Hirai, H. Differently spliced cDNAs of human leukocyte tyrosine kinase receptor tyrosine kinase predict receptor proteins with and without a tyrosine kinase domain and a soluble receptor protein. Proc. Nat. Acad. Sci. 90: 5404-5408, 1993. [PubMed: 7685902] [Full Text: https://doi.org/10.1073/pnas.90.12.5404]