Disease relevance of Ltk

• Cell line 101 is a thymidine kinase (TK)-positive derivative of Ltk- which contains ca. 20 copies of the herpes simplex virus TK gene organized in a tandem array [1].
• Differential recruitment of viral and allo-epitopes into the MHC class I antigen processing pathway of a novel mutant of Ltk- cells. HSV/MHC class I restriction/immune recognition/antigen processing/antigen presentation/influenza virus [2].
• Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3 [3].
• Neither the IE68 nor IE94 proteins could be detected by biochemical labelling procedures in infected mouse Ltk- or F9 teratocarcinoma stem cells, although IE94 was synthesized after retinoic acid-induced differentiation of the F9 cells [4].
• Rescue of hepatitis A virus from cDNA-transfected but not virion RNA-transfected mouse Ltk- cells [5].

High impact information on Ltk

• Ltk resembles a receptor tyrosine kinase; it has a short, glycosylated, and cysteine-rich N-terminal domain [6].
• Indirect immunofluorescence and immunogold staining of COS transfectants and endoglycosidase analysis of both COS transfectants and lymphocytes indicate the unusual localization of Ltk to the endoplasmic reticulum (ER) [6].
• The subcellular localization of the mouse Ltk transmembrane protein tyrosine kinase was studied in transfected COS cells, a mature B lymphocyte line, and a low expressing transfected lymphocyte clone [6].
• Through a series of electrophoretic fractionations in concert with transfection assays, we isolated a 3.4 kb fragment which contains the thymidine kinase gene and which alone is competent in the biochemical transformation of Ltk- cells [7].
• Ltk is expressed at a very low level in only a few cell lines and tissues and may be the receptor for a pre-B lymphocyte growth or differentiation factor, because 10 tested pre-B lines each contained 2.4 and 2.8 kb mRNAs [8].

Biological context of Ltk

• Receptor tyrosine kinase gene Tyro3 maps to mouse chromosome 2, closely linked to Ltk [9].
• Cell lines derived from the murine Ltk- cell were found useful in exploring the contribution of cAMP-dependent phosphorylation in V2 vasopressin receptor desensitization [10].
• We further report that a DSB in the genome of a mouse Ltk- cell is repaired preferentially by non-homologous end-joining rather than by targeted homologous recombination with an exogenous donor sequence [11].
• After replication, half of them were tested for expression of a new phenotype: an adenylyl cyclase stimulatory receptor not normally expressed in the Ltk- recipient cell [12].
• Agonist stimulation of Mel1c(alpha) receptor was associated with the inhibition of cAMP accumulation stimulated by forskolin (IC50 approximately 10(-10) M) in HeLa, Ltk-, and human embryonic kidney 293 (HEK 293) cells [13].

Anatomical context of Ltk

• Leukocyte tyrosine kinase (LTK) is a receptor tyrosine kinase which belongs to the insulin receptor superfamily and is mainly expressed in pre-B lymphocytes and neuronal tissues [14].
• Ltk was also expressed in adult, but not in embryonic, mouse brain, and immunostaining detected the protein in essentially all neurons of the cerebral cortex and hippocampus, but not in the cerebellum [8].
• To analyze why this Ltk isoform is retained in the endoplasmic reticulum, we investigated its behavior in over-expressing cells [15].
• Ltk is a new member of the ros/insulin receptor family of tyrosine kinases that is expressed in murine B-lymphocyte precursors and forebrain neurons [16].
• As in oocytes, expression of Kv1.4 in HEK-293, Ltk- or neonatal rat ventricular cells reveals rapidly activating K+ currents [17].

Associations of Ltk with chemical compounds

• The 2.6-kilobase fragment was detected in the primary and secondary transfectants but not in the parental Ltk-, Adriamycin-resistant Ltk-, and Adriamycin-resistant P388 cells [18].
• Spleen cells of CH3 mice immunized against the influenza nucleoprotein peptide 50-63 (NP 50-63) were restimulated in vitro (i) with peptide-pulsed syngeneic fibroblast cells (Ltk-) as antigen-presenting cells, which were in addition (ii) infected with NDV or (iii) stably transfected with the HN cDNA of NDV [19].
• A mouse cell line (Ltk-aprt-) which is resistant to the anti-viral effects of interferon also has a reduced ability to synthesize metallothionein on exposure to cadmium [20].
• The intrinsic activities of selected dopamine D1 receptor agonists were compared in three distinct molecular expression systems, C-6, Ltk, and GH4 cells transfected with primate D1A receptors [21].
• One peak of TK activity with an Rm value of 0.8-0.9, corresponding to mitochondrial TK, was observed on polyacrylamide gel electrophoresis of Ltk- cell extracts [22].

Other interactions of Ltk

• A mouse fibroblast cell-line deficient in thymidine kinase (Ltk(-) aprt(-)) fails to show an anti-viral response when treated with interferon [23].
• The cryptic promoter, further localized within a 153-bp fragment (fr153BN), exerted its effect in Ltk- and H-ras-transformed NIH3T3 (3T3-Hras) but not in parental NIH3T3 cells [24].
• We have characterized the IFN responses of a mutant murine cell line (Ltk-aprt-) which is unable to mount an antiviral response when treated with IFN-beta [25].
• Cotransfection of the Lyt-3a gene together with a cloned Lyt-2a gene resulted in expression of both Lyt-2 and Lyt-3.1 on the surface of Ltk- and BW5147 cells.(ABSTRACT TRUNCATED AT 250 WORDS)[26]
• The putative MAR co-localized in the fragile domain with genes important to the hemopoietic system (leukocyte tyrosine kinase, zinc finger protein 106, erythrocyte protein band 4.2, and beta(2)-microglobulin (beta2m)); the beta2m subdomain was a particular focus of breakage [27].

Analytical, diagnostic and therapeutic context of Ltk

• Southern blot analysis demonstrated that switch recombination caused the deletion of the Htk gene in all pre-B clones examined while the loss of Htk in Ltk- clones was not mediated by S region recombination [28].
• 3. In whole-cell recordings with Ltk- cells, a brief (3-5 min) application of ET-1 (10(-10) M) induced a sustained inward current at a holding potential of -60 mV [29].
• In agreement with this, Northern blot and nuclear run-on analyses show that the induction of transcription of three distinct genes (2,5(A) synthetase, BS-I-150, and BS-II-4) is blocked in Ltk-aprt- cells whereas another gene (I-8) is activated normally [25].
• The idea that spare receptors are one important determinant of observed intrinsic activity was explored directly by "receptor titration," in which ca. 90% of D1 receptors in Ltk cells were inactivated using EEDQ, an irreversible antagonist [21].
• The presence of lysosomal acid phosphatase (LAP) in coated pits at the plasma membrane was investigated by immunocytochemistry in thymidine kinase negative mouse L-cells (Ltk-) and baby hamster kidney (BHK) cells overexpressing human LAP (Ltk-LAP and BHK-LAP cells) [30].

References