Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression patterns of low and high molecular weight cytokeratins (LCK and HCK) vimentin and desmin were investigated by immunocytochemistry in the rete testis and epididymis in the dog. The epithelium of the rete testis displayed coexpression of LCK, vimentin and desmin. The epithelium of the efferent ductules was composed of ciliated and nonciliated cells; the ciliated cells expressed LCK strongly. The epithelium of the epididymal duct was composed of principal, apical and basal cells. Principal cells in the duct of the head of the epididymis displayed LCK and vimentin, with a predominance of LCK in the apical cytoplasmic regions and vimentin in the basal portions of the cells. Expression of vimentin in the principal cells decreased towards the body of the epididymis and disappeared in the tail region, where LCK remained unchanged. Apical cells of the epididymal duct expressed LCK. Basal cells in the duct of the head and body of the epididymis showed LCK and those of the duct of the body of the epididymis also HCK expression.
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PMID:Coexpression of different cytokeratins, vimentin and desmin in the rete testis and epididymis in the dog. 751 42

T lymphocytes require two signals to be activated. The antigen-specific T-cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7-2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein-tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72ITK/EMT) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72ITK/EMT is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72ITK/EMT. Thus, tyrosine phosphorylation of p72ITK/EMT may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72ITK/EMT, and by analogy other members of the Tec family, responds to extracellularly generated signals.
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PMID:CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line. 752 75

Identification and characterization of the cellular proteins that specifically bind to the immunosuppressive drugs, cyclosporine (CsA), FK506, and rapamycin is necessary to understand their mechanism of action. We have isolated and partially characterized a 52 kDa binding protein (BP) from calf thymus. Using 12 peptide substrates we observed very low or no cis-trans peptidyl prolyl isomerase activity. We further tested the protein for catalytic activity including kinase activity, phosphatase activity, protein kinase C regulation, and LCK tyrosine kinase regulation. The 52 kDa BP was capable of blocking the cyclic AMP dependent, protein kinase mediated, phosphorylation of histones and casein. The protein did not demonstrate kinase activity, nor did it affect the activity of protein kinase C or LCK tyrosine kinase. Microsequencing of the 52 kDa BP was performed. A comparison of known sequences indicated that the protein is unique and has not been previously characterized.
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PMID:Partial characterization of a 52 kDa CsA/FK506/rapamycin binding protein. 753 57

The human receptor Fc gamma RIIA for the Fc portion of IgG (Fc gamma) was expressed in a human T-cell line and conferred on these cells the ability to perform IgG antibody-stimulated phagocytosis. Crosslinking Fc gamma RIIA with anti-Fc gamma RII monoclonal antibody also induced tyrosine phosphorylation of multiple proteins including Fc gamma RIIA, ZAP-70, p72SYK, and phospholipase C gamma 1 subunit and an increase in intracellular Ca2+ concentration. The T cell receptor-associated zeta-chain was not tyrosine-phosphorylated after crosslinking of Fc gamma RIIA, suggesting that the Fc gamma RIIA-mediated signals were independent of CD3. Fc gamma RIIA-mediated signal transduction was defective in a transfected mutant T-cell line exhibiting reduced expression of the tyrosine kinases LCK and FYN. These studies indicate that certain T cells can assume phagocytic properties after transfection of cDNA encoding an Fc gamma receptor with the capability of inducing a phagocytic signal.
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PMID:Transfection of an Fc gamma receptor cDNA induces T cells to become phagocytic. 793 68

Previously we had characterized the t(1;7)(p34;q34) translocation from HSB-2. This translocation fused the beta T-cell receptor gene (TCRB) constant region and transcriptional enhancer with the type I transcription unit of the LCK gene on the derivative 1 [der(1)] chromosome. The type II promoter was translocated to the der(7) chromosome. Regarding the mechanism of the t(1;7) in HSB-2, we identified an alternating purine-pyrimidine tract (G-T)17 at the 1p34/LCK breakpoint. Additionally, sequence analysis of both breakpoint junctions provided data that implicate the V(D)J recombinase in formation of the t(1;7). A heptamer-nonamer recognition sequence with a 12-bp spacer was found in the immediate vicinity of the 1p34/LCK breakpoint and, thus, chromosomal breakage at 1p34 may be explained as resulting from recombinase activity. Because phosphorylation of Tyr-505 in vivo regulates the tyrosine kinase activity of p56lck we amplified a region from LCK exon 12 that contains the codon for Tyr-505 and showed no mutation of this codon in HSB-2 DNA and, therefore, p56lck in HSB-2 is not activated by mutation of Tyr-505. We have analyzed LCK gene expression in HSB-2 and SUP-T12 cell lines. RNase protection analysis identified almost exclusively type I transcripts in HSB-2. An independent t(1;7) in SUP-T12 also resulted in the juxtaposition of LCK to TCRB. The breakpoint in SUP-T12 occurred 2 kb 5' of the type II promoter, leaving an intact LCK gene on the der(1) chromosome. RNase protection analysis identified both type I and type II LCK transcripts in a 3:1 ratio in SUP-T12. Factors other than proximity to the TCRB enhancer must affect promoter utilization in this cell line.
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PMID:Molecular analysis of the T-cell acute lymphoblastic leukemia-associated t(1;7)(p34;q34) that fuses LCK and TCRB. 804 39

The LCK gene encodes a lymphocyte-specific member of the Src family of protein tyrosine kinases. This gene was previously assigned to human chromosome region 1p35-->p32 by isotopic in situ hybridization. We report here its more refined localization to bands 1p35-->p34.3 by fluorescence in situ hybridization on R-banded metaphase chromosomes and its mapping relative to the reference marker pYNZ2 (D1S57).
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PMID:Subregional mapping of the human lymphocyte-specific protein tyrosine kinase gene (LCK) to 1p35-->p34.3 and its position relative to the 1p marker D1S57. 806 94

DNA probes for the NRAS, HRAS, KRAS2, LCK, RAF1, MET, MYCL1, MYCN, MYB, ERBB2, FOS, CSF1R, and SRC protooncogene loci; the retinoblastoma gene locus (RB1); the tumor virus integration sites INT2, PVT1, and MLV12; and the locus of the tumor-specific antigen T1A were used to screen mouse genomic DNAs from RF/J, CAST/Ei, MOLF/Ei, Mus musculus musculus, M. m. poschiavinus, and M. spretus. Polymorphic DNA fragments for the 18 DNA probes have been identified using Southern blot hybridization and restriction fragment length polymorphism (RFLP) analysis.
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PMID:Novel RFLPs at protooncogene and cancer-related gene loci on mouse chromosomes. 809 10

The tyrosine protein kinase p56lck transduces signals important for antigen-induced T-cell activation. In transgenic mice, p56lck is oncogenic when overexpressed or expressed as a mutant, catalytically activated enzyme. In humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34) chromosomal translocation. This translocation positions the beta T-cell receptor constant region enhancer upstream of the LCK gene without interrupting the LCK coding sequences, and a translocation of this sort occurs in both the HSB2 and the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck protein in HSB2 cells is elevated approximately 2-fold in comparison with that in normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted from mutations in the LCK gene that activated its function as a phosphotransferase and converted it into a dominant transforming oncogene. The oncogenic p56lck in HSB2 cells contained one amino acid substitution within the CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts, three of these mutations cooperated to produce the fully oncogenic form of this p56lck variant. These results suggest that mutation of LCK may contribute to some human T-cell leukemias.
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PMID:Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. 813 46

Previous studies have indicated that interaction of Fc gamma RIIIA on natural killer (NK) cells with various immunoglobulin ligands or monoclonal antibodies (mAbs) can have either stimulatory or inhibitory effects on cytotoxic activity, but the basis for such divergent functional effects has been unclear. We report here that stimulation of NK cells via Fc gamma RIIIA by monoclonal anti-human CD16 (3G8), monomeric IgG (mIgG), or dimeric IgG (dIgG), used either alone or cross-linked by secondary Ab (goat anti-mouse IgG or goat anti-human IgG), resulted in different phosphotyrosine protein patterns. These results suggest that distinct substrates are involved in signaling pathways activated via various agonists of the same triggering surface molecule. Three protein tyrosine kinases, i.e., LCK, LYN, and SYK, were activated by occupancy of the Fc gamma RIIIA, and only LCK activity showed a divergence in effects induced by the various ligands, with strong autophosphorylation induced by mIgG upon cross-linking. We observed no ligand-induced activation of p59fyn, p60c-src, or p62c-yes, src-related protein tyrosine kinases which are expressed in NK cells. Activity of phosphatidylinositol 3-kinase (PI 3-kinase) induced by receptor-specific antibodies or IgG ligands had different kinetics while the level of cytoplasmic free calcium was greatest upon 3G8-induced stimulation. Although the changes in kinase activities associated with Fc gamma RIIIA-mediated regulation of NK cells are complex, it appears that the patterns induced varied with the nature of the ligand and the direction of the regulation of NK activity.
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PMID:Divergent phosphotyrosine signaling via Fc gamma RIIIA on human NK cells. 854 46

Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.
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PMID:The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT. 860 88


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