Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipocytic-cytosolic non-receptor protein tyrosine kinase (CytPTK) when activated can substitute for the insulin receptor tyrosine kinase (InsRTK), in manifesting several insulin effects in insulin-receptor independent fashion. Our aims here were to utilize PolyGlu4Tyr, a good experimental exogenous substrate for protein tyrosine kinases (PTKs) in general, for studying qualitative and quantitative parameters of CytPTKs extracted from different tissue cytosols. At the same time, we would search for a unique specific marker specifically characterizing CytPTKs. High speed supernatants of spleen, thymus, smooth muscle, lung and kidney were found to be rich in CytPTK activities. Their specific activities being 6- to 13-fold that of liver or adipose cytosols. Brain, testis and adrenal cytosols were an intermediate source of CytPTK activity, whereas CytPTK activity of heart and skeletal muscle was low. It was also evaluated that the capacity of the cytosol to phosphorylate PolyGlu4Tyr is 15-50% that of the non-stimulated Triton X-100 extractable plasma membrane PTKs. Fractionation of the cytosols on superose 12 column revealed several CytPTKs within the same tissue, their peaks ranging between 30 and 450 kDa. Immunoblotting analysis showed Fyn and Lyn were present in most tissue cytosols. Upon immunoprecipitation, however, with anti-Fyn or anti-Lyn, negligible amounts (< 2%) of the total cellular CytPTK were precipitated. Thus, these general markers of CytPTKs comprise only a minor proportion of the total intracellular PolyGlu4Tyr phosphorylating capacity. To see whether a specific marker for CytPTK could be detected, we also examined the requirement of CytPTKs for divalent ions, their preferred phosphate donor and their sensitivity to inhibition by known PTK inhibitors. We found that the order of reactivity with divalent cations was Co2+ > Mn2+ > Mg2+, while Zn2+ and Ca2+ did not support CytPTK activity. The best phosphate donor was ATP (ED50 = 5 microM), but other nucleoside 3-phosphates could substitute for ATP at high concentrations. With respect to these parameters, no basic difference exists between cytosolic and plasma-membrane PTKs. The PTK inhibitors, genestein and quercetin, inhibited both cytosolic and membranal PTKs at micromolar concentrations. In contrast, staurosporine was a potent inhibitor of CytPTKs (IC50 5-20 nM) and a poor inhibitor of membranal PTKs (IC50 10-40 microM). One of the conclusions we can draw from this study is that tissue cytosols contain PolyGlu4Tyr phosphorylating capacity in quantities greater than previously assumed and that the low level of phosphotyrosine found in cells is not the result of limited intracellular levels of CytPTKs.
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PMID:Non-receptor cytosolic protein tyrosine kinases from various rat tissues. 749 84

The Flt3 gene encodes a tyrosine kinase receptor highly related to the Kit and Fms gene products. We have studied the expression of Flt3 by using in situ hybridization of mouse tissue sections. The results show that Flt3 RNAs are present in certain regions of lymphohematopoietic organs, placenta and nervous system. Flt3 is expressed in the medullary area of fetal and newborn thymus, in the paracortical regions of lymph nodes and in the red pulp of spleen. In placenta, labyrinthine trophoblasts express Flt3. Finally, Flt3 RNAs are found in several regions of the brain and in cerebellar Purkinje cells. Western-blot analysis showed that the FLT3 protein is present in the tissues positive for Flt3 RNA expression. Our observations allow for a comparison with the distribution of the Kit gene and analysis of a possible redundancy between KIT and FLT3 receptors.
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PMID:Expression of Flt3 tyrosine kinase receptor gene in mouse hematopoietic and nervous tissues. 762 10

The T cell receptor (TcR) V beta-specific expansion, deletion and induction of nonresponsiveness among murine T cells responding to superantigens in the periphery has been well characterized. Here we demonstrate that clonal deletion of staphylococcal enterotoxin (SE) B-reactive V beta 8.2+ cells can be significantly increased when mice are injected with hydrocortisone (HC) following superantigen stimulation in vivo. The induced sensitivity to HC persists for at least 30 days after SEB injection, making it unlikely that proliferating cells were uniquely responsible for the enhanced deletion. Superantigen-induced HC sensitivity was a general phenomenon and could also be observed among V beta 11+ cells after the injection of SEA. Experiments conducted on thymectomized mice indicated that HC-sensitive, SEB-responsive cells could not be accounted for by rapidly produced, immature lymphocytes recently exported from the thymus. Further, V beta 8.1+ peripheral lymphocytes from TcR transgenic mice expressing the Mls-1a superantigen were sensitive to HC. These results imply that the majority of cells remaining after superantigen-induced clonal expansion and deletion in vivo have indeed reacted with the superantigen. Implications for differential superantigen recognition by T cells expressing the same TcR V beta domain, perhaps due to a significant V alpha contribution to the interaction in vivo, are discussed.
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PMID:Peripheral clonal deletion of superantigen-reactive T cells is enhanced by cortisone. 767 51

A protein receptor tyrosine kinase (RTK 6) has been isolated from a complementary DNA library of SKOV-3, an epithelial ovarian cancer cell line, using a polymerase chain reaction (PCR)-mediated approach. The primary structure of the predicted amino acid sequence of the protein shows a novel NH2-terminal region which has homology to a factor VIII-like domain. The juxtamembrane region is proline and glycine rich and is the longest for any known receptor kinase. The COOH-terminal catalytic domain has all of the canonical sequence motifs of a receptor tyrosine kinase with homology to the TRK-2H protein (49%). A single transcript of 4.5 kilobases is expressed at low levels in heart, placenta, lung, liver, muscle, kidney, and pancreas, with high levels of expression in the brain. Ribonuclease protection assay showed a varying level of expression of message in a panel of eight ovarian cancer cell lines compared to placenta. In situ hybridization analysis demonstrated localization of mRNA in the epithelial cells of the ovary, kidney, small bowel, lung, thymus, and brain. There was a lower level of message in normal, benign, and borderline tumors of the ovary compared to malignant tumors of the ovary. Polyclonal antisera raised against a COOH-terminal synthetic peptide recognize a M(r) 140,000 protein in ovarian cancer cells, which autophosphorylates in an in vitro kinase assay.
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PMID:Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line. 784 19

B61 was originally described as a novel secreted tumor necrosis factor-alpha-inducible gene product in endothelial cells (Holzman, L. B., Marks, R. M., and Dixit, V. M. (1990) Mol. Cell. Biol. 10, 5830-5838). It was recently discovered that soluble recombinant B61 could serve as a ligand for the Eck receptor protein-tyrosine kinase, a member of the Eph/Eck subfamily of receptor protein-tyrosine kinases (Bartley, T.D., Hunt, R. W., Welcher, A. A., Boyle, W. J., Parker, V. P., Lindberg, R. A., Lu, H. S., Colombero, A. M., Elliott, R. L., Guthrie, R. A., Holst, P. L., Skrine, J. D., Toso, R. J., Zhang, M., Fernandez, E., Trail, G., Yarnum, B., Yarden, Y., Hunter, T., and Fox, G. M. (1994) Nature 368, 558-560). We now show that B61 can also exist as a cell surface glycosylphosphatidyl-inositol-linked protein that is capable of activating the Eck receptor protein-tyrosine kinase, the first such report of a receptor protein-tyrosine kinase ligand that is glycosylphosphatidylinositol-linked. In addition, the expression patterns of B61 and Eck during mouse ontogeny were determined by in situ hybridization. Both were found to be highly expressed in the developing lung and gut, while Eck was preferentially expressed in the thymus. Finally, the gene for B61 was localized to a specific position on mouse chromosome 3 by interspecific back-cross analysis.
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PMID:Characterization of B61, the ligand for the Eck receptor protein-tyrosine kinase. 789 Jun 84

A wide range of growth and differentiation processes are regulated by the signalling of receptor tyrosine kinases (RTKs). We have developed a nested polymerase chain reaction (PCR) procedure with degenerate primers, and used it to identify RTKs expressed in murine fetal thymus. A novel RTK, called FLT4, and the murine homologue of FLT were found, and their PCR fragment sequences were used to isolate larger cDNA clones spanning the complete coding regions of these receptors. FLT4 was found to contain an extracellular region similar to the corresponding sequences of FLT and Flk-1, containing seven immunoglobulin domains.
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PMID:Molecular cloning of murine FLT and FLT4. 839 64

One cDNA clone (G7) was isolated from a lambda gt11 human liver cDNA library by the reaction with a serum containing anti-dsDNA Abs and was ligated into pGEX-1 lambda T vector. All the 10 SLE sera with anti-dsDNA, 2 samples of human monoclonal anti-dsDNA (33.C9 and 33.H11), and 2 affinity-purified anti-dsDNA Abs recognized the glutathione S-transferase fusion protein expressed by G7 (G7-FP). Ab binding to the recombinant protein expressed by G7 (G7-RP) and to G7-FP was inhibited completely by calf thymus dsDNA. The cDNA was 1314 nucleotides in length and contained an open reading frame encoding 352 amino acids. However, it seems to be a partial length cDNA because the affinity-purified Ab from G7-FP recognized only a 104-kDa protein on Western blot using MOLT4 cell extract. The nucleotide sequence of G7 was homologous (99% identity) to a cDNA encoding human ribosomal protein (r-protein) S1 homologue mRNA. The encoded protein contains repeating residues as a feature of r-proteins S1. Cytoplasmic and nucleolar staining of 33.H11 on indirect immunofluorescence (IF) using HEP 2 cells was inhibited by both G7-RP and calf thymus dsDNA. On ELISA, 33.H11 had a higher affinity for G7-RP than for DNA while 33.C9 had a higher affinity for DNA than for G7-RP and binds nuclei on IF. We conclude that G7 encodes a portion of human r-protein S1 and anti-dsDNA Abs cross-react with this protein.
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PMID:Lupus autoantibodies to double-stranded DNA cross-react with ribosomal protein S1. 856 74

A fourth member of the diacylglycerol kinase (DGK) gene family termed DGK delta was cloned from the human testis cDNA library. The cDNA sequence contains an open reading frame of 3,507 nucleotides encoding a putative DGK protein of 130,006 Da. Interestingly, the new DGK isozyme contains a pleckstrin homology domain found in a number of proteins involved in signal transduction. Furthermore, the C-terminal tail of this isozyme is very similar to those of the EPH family of receptor tyrosine kinases. The primary structure of the delta-isozyme also has two cysteine-rich zinc finger-like structures (C3 region) and the C-terminal C4 region, both of which have been commonly found in the three isozymes previously cloned (DGKs alpha, beta and gamma). However, DGK delta lacks the EF-hand motifs (C2) and contains a long Glu- and Ser-rich insertion (317 residues), which divides the C4 region into two portions. Taken together, these structural features of DGK delta indicate that this isozyme belongs to a DGK subfamily distinct from that consisting of DGKs alpha, beta, and gamma. Increased DGK activity without marked preference to arachidonoyl type of diacylglycerol was detected in the particulate fraction of COS-7 cells expressing the transfected DGKdelta cDNA. The enzyme activity was independent of phosphatidylserine, which is a common activator for the previously sequenced DGKs. Northern blot analysis showed that the DGK delta mRNA (approximately 6.3 kilobases) is most abundant in human skeletal muscle but undetectable in the brain, thymus, and retina. This expression pattern is different from those of the previously cloned DGKs. Our results show that the DGK gene family consists of at least two subfamilies consisting of enzymes with distinct structural characteristics and that each cell type probably expresses its own characteristic repertoire of DGKs whose functions may be regulated through different signal transduction pathways.
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PMID:Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases. 862 38

Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hematopoietic system and compared the pattern of expression with that of Ufo. Both receptors were abundantly expressed in differentiating embryonic stem cells, yolk sac blood islands, para-aortic splanchnopleural mesoderm, fractionated AA4+ fetal liver cells, and fetal thymus from day 14 until birth. Although Ufo was expressed at moderate levels in adult bone marrow, expression of Dtk in this tissue was barely detectable. In adult bone marrow subpopulations fractionated using counterflow centrifugal elutriation, immunomagnetic bead selection for lineage-depletion and FACS sorting for c-kit expression, very low levels of Dtk and/or Ufo were detected in some cell fractions. These results suggest that Dtk and Ufo are likely to be involved in the regulation of hematopoiesis, particularly during the embryonic stages of blood cell development.
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PMID:The Dtk receptor tyrosine kinase, which binds protein S, is expressed during hematopoiesis. 864 60

Peritoneal lymphocytes (PCL) of 45 healthy individuals, four uremic patients with end-stage renal disease (ESRD) and 25 long-term continuous ambulatory peritoneal dialysis (CAPD) patients were characterized by flow cytometry to investigate whether CAPD alters the phenotype of PCL. B lineage cells constitute a minority of PCL (2.5% of cells). Although the majority of peritoneal T cells expressed alpha beta T cell receptor (TcR), 7% expressed gamma delta TcR, a proportion which was significantly higher than that in peripheral blood (PBMC) (approximately 4%). The majority of PCL T cells exhibited markers of the thymus-dependent lineage (CD2, CD3, TcR alpha beta, CD8 alpha beta or CD4) and surface antigens associated with memory and activation (CD45RO, CD11a, CD18, CD49d, HLA-DR). An average of 75% of both CD4+ and CD8+ PCL T cells of healthy subjects and CAPD patients were CDw60+, thus characterizing the T cell subset containing the helper activity for the mitogen-driven B cell differentiation. CD44s was abundantly expressed on PCL T cells. In contrast to PCL T cells of healthy subjects peritoneal T lymphocytes of CAPD patients exhibited CD44 splice variants containing products of exon-v9 and the proportion of CD44v9+ cells correlated with the frequency of peritonitis episodes the patients had gone through. The majority of PCL T cells of both healthy subjects and CAPD patients were CD8+. A large proportion of CD8+ PCL T cells from healthy subjects expressed the homodimeric CD8 alpha alpha isoform; however, such cells were not found in CAPD patients. In healthy subjects mRNA for the recombination activating gene 1 (RAG-1) was detectable in a PCL population containing CD7-CD34+ and CD7+CD34+ cells. In contrast, neither mRNA transcripts of the RAG-1 gene nor CD34+ cells were detectable in PCL of CAPD patients.
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PMID:Continuous ambulatory peritoneal dialysis impairs T lymphocyte selection in the peritoneum. 873 Nov 4


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