Disease relevance of LTK

• ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK) [1].
• Protein tyrosine kinase activity is essential for Fc gamma receptor-mediated intracellular killing of Staphylococcus aureus by human monocytes [2].
• Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p210(bcr-abl) protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase [3].
• The 36-kD protein-tyrosine kinase substrate p36 has been variously postulated to be involved in membrane-cytoskeletal interactions, membrane traffic, and the regulation of phospholipase A2, and its phosphorylation may play some role in malignant transformation by avian sarcoma viruses [4].
• Antigen receptor-mediated protein tyrosine kinase activity is regulated by a pertussis toxin-sensitive G protein [5].

Psychiatry related information on LTK

• Cytosolic protein tyrosine kinase activity in Alzheimer's disease tissue was not significantly different from that in control tissue [6].

High impact information on LTK

• Src, the product of the first characterized proto-oncogene and the first identified protein tyrosine kinase, plays a critical role in the signal transduction of G protein-coupled receptors [7].
• Many cellular recognition events in the immune system are initiated by aggregation of cell surface receptors that lack intrinsic protein-tyrosine kinase activity [8].
• Complementary DNAs were cloned and found to be virtually identical to tyk2, a human mRNA encoding a non-receptor protein tyrosine kinase of previously unknown function [9].
• ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain [10].
• Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn) [11].

Chemical compound and disease context of LTK

• Permanent murine fibroblasts (LTK-) were transfected with a dimer of hepatitis B virus (HBV) DNA and a neomycin resistance gene which were both linked to the simian virus 40 (SV40) early promoter/enhancer [12].
• PURPOSE: To assess the safety and efficacy of noncontact holmium:yttrium aluminium garnet laser thermal keratoplasty (Ho:YAG LTK) for correction of low to moderate hyperopia [13].
• Administration of protein tyrosine kinase inhibitors and gemcitabine also significantly decreased the incidence of lymph node and liver metastasis [14].
• Effect of human immunodeficiency virus gp120 glycoprotein on the association of the protein tyrosine kinase p56lck with CD4 in human T lymphocytes [15].
• The enhanced binding of C3bi-coated erythrocytes and B. pertussis to monocytes could be markedly inhibited by tyrphostin-47, a protein tyrosine kinase inhibitor [16].

Biological context of LTK

• To identify novel protein tyrosine kinase (PTK) genes expressed in human lymphoid cells, we have screened B- and T-cell cDNA libraries at low stringency using a c-fms tyrosine kinase domain probe [17].
• Three new PTK genes were identified, based on the presence of conserved amino acid sequence motifs characteristic of the catalytic domain of tyrosine kinases [17].
• In contrast, none of these signal transducer proteins were associated with a kinase-negative ltk mutant (K544M-ltk) in which methionine at the putative ATP binding site was replaced with lysine [18].
• Here we report the cloning of a human LTK cDNA clone containing the complete open reading frame of a putative receptor tyrosine kinase protein [19].
• By using Ba/F3 cells expressing epidermal growth factor receptor-LTK chimeric receptors containing a mutation at each NPXY site, we showed that while both NPXY motifs equally contribute to activation of the Ras pathway and generation of mitogenic signals, only tyrosine 485 of LTK transmits cell survival signals [20].

Anatomical context of LTK

• To identify the cellular signal transducer proteins binding to the ltk protein, we have analysed the recombinant ltk protein transiently expressed in COS cells [18].
• Stimulation of the T-cell antigen receptor (TCR), which itself is not a protein-tyrosine kinase (PTK), activates a PTK and phospholipase C (PLC) [21].
• LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues [22].
• These results indicate that inhibition of PTK impairs the oxygen-dependent bactericidal mechanisms of monocytes [2].
• We have produced a cell line which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response [23].

Associations of LTK with chemical compounds

• Recently we have cloned a full sized human ltk cDNA which has a 423 amino acid extracellular domain which may bind to unknown ligand(s), and a 415 amino acid cytoplasmic domain which contains a tyrosine kinase domain [18].
• Furthermore, the wild-type ltk protein also binds to a serine/threonine kinase, Raf-1, in vivo [18].
• We show here that genistein, an inhibitor of protein tyrosine kinase, blocks VEGF induction [24].
• Pretreatment with herbimycin A, a PTK inhibitor, blocked the Fc gamma R-induced tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2, and the subsequent release of inositol phosphates [25].
• The results showed that phagocytosis of bacteria by monocytes was not affected by the PTK inhibitors genistein and tyrphostin-47 [2].

Physical interactions of LTK

• The results obtained indicate that the protein tyrosine kinase Syk interacts with multiple CD22-derived phosphopeptides in both immunoprecipitation and reverse Far Western assays [26].
• However, a PTK active mutant unable to bind PLCgamma did not show defects in transformation activity [27].
• The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex [28].
• These data provide evidence that BCR couples the cytoplasmic protein-tyrosine kinase and RAS signaling pathways [29].
• In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck [30].

Enzymatic interactions of LTK

• Herein, we find that hTAF(II)68 is phosphorylated on tyrosine residue(s) by ectopic expression of v-Src protein tyrosine kinase in vitro and in vivo [31].
• When self-phosphorylated EGF receptor was fractionated by Sephacryl S-300 gel permeation chromatography, the peak of PtdIns kinase activity was separated from the comigrating peak of protein-tyrosine kinase activity and the self-phosphorylated EGF receptor [32].
• Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP [33].
• MB-1 is also phosphorylated in immune complexes prepared with antibodies to PTK72, indicating that components of the IgM complex are associated with PTK72 [34].
• Functional analysis of this molecule determined that activated Fc gamma RIIA is tyrosine phosphorylated and that activation induced the physical association with the protein tyrosine kinase p72syk [35].

Regulatory relationships of LTK

• The human and rat FER genes encode a widely expressed 94-kilodalton protein-tyrosine kinase which is antigenically related to the fps/fes protein-tyrosine kinase [36].
• The CRF-induced phosphorylation was inhibited by the protein tyrosine kinase inhibitors genistein and herbimycin A, suggesting that CRF activates protein tyrosine kinases [37].
• In the present study we reconstituted the LAT signalling pathway by demonstrating that a direct tyrosine phosphorylation of LAT with activated protein-tyrosine kinase Zap70 is necessary and sufficient for the association and activation of signalling proteins [38].
• Cross-linking of CD43 induced tyrosine phosphorylation of several intracellular molecules including the protein tyrosine kinase Syk, the proto-oncogene product Cbl, and phospholipase C (PLC)-gamma2 in MO7e cells [39].
• The data also suggest that CD4-associated protein tyrosine kinase p56lck could up-regulate defective CD3-mediated induction of phospholipase C activity by increasing tyrosine phosphorylation of phospholipase C-gamma 1 [40].

Other interactions of LTK

• The deduced amino acid sequences reveal that ALK is a novel receptor protein-tyrosine kinase having a putative transmembrane domain and an extracellular domain [41].
• The EGF receptor possesses intrinsic protein tyrosine kinase activity which is essential for signal transduction [42].
• These data suggest that IRS-1 possesses anti-apoptotic function at least in LTK signaling [20].
• This rearrangement was shown to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23 [43].
• A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6 [44].

Analytical, diagnostic and therapeutic context of LTK

• This is the first detection of cytoplasmic signal transducers that bind to the ltk protein in vivo [18].
• TCR stimulation leads to an association between the SH2 domains of PLC gamma 1 and a protein tyrosine kinase, which, by peptide mapping, is identical to p56lck [45].
• To investigate potential mechanisms for this, IL-9 was assessed for effects on protein tyrosine kinase activities in M07e cells by immunoblotting with anti-phosphotyrosine monoclonal antibody; results were compared with those of Steel factor alone and in combination with IL-9, and those of 12-0-tetradecanoyl phorbol-13-acetate (TPA) [46].
• A major target of the immunosuppression was the IL-2R-associated protein tyrosine kinase, Janus kinase 3 (Jak3) [47].
• Transfection of the cDNA for the alpha chain of the human IL-2R into LTK- mouse fibroblast cell line (L3 cells) leads, in long-term cultures, to the formation of transcripts of endogenous mouse IL-2, IL-2R alpha and beta genes, as detected by Northern blotting [48].

References