Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the role of proline-rich tyrosine kinase (Pyk) 2 in the spreading and migration of human blood eosinophils after beta(2)-integrin ligation. Western blot analysis showed that Pyk2 was activated by phosphorylation at Y402 after eosinophil adhesion to BSA-coated plates after activation with IL-5, platelet-activating factor (PAF), formyl-met-leu-phe (fMLP), or Mn(2)(+). To determine the role of Pyk2 in regulating eosinophil migration, we used a transducable dominant-negative inhibitor of Pyk2, TAT-mediated protein transduction of dominant-negative C-terminal Pyk2 (TAT-Pyk2-CT), a fusion protein in which TAT peptide was fused to the C-terminal Pyk2. TAT-Pyk2-CT blocked tyrosine phosphorylation of Pyk2 caused by beta(2)-integrin adhesion, but did not block adhesion of eosinophils to plated BSA. TAT-Pyk2-CT also blocked subsequent spreading and migration of eosinophils caused by IL-5, PAF, or fMLP. Spreading eosinophils stained with FITC-conjugated phalloidin showed elongation and formation of multiple fillopodia and lamellipodia, whereas nonspreading eosinophils were smaller and round. Treatment of eosinophils with TAT-Pyk2-CT had no effect on the initial cell polarization, but blocked the formation of fillopodia and lamellipodia in adherent cells. Migration of eosinophils through Transwell plates caused by IL-5, PAF, or fMLP was blocked significantly after inhibition of Pyk2. These data indicate that Pyk2, although not involved in beta(2)-integrin adhesion, causes eosinophil spreading and regulates subsequent chemotactic migration after beta(2)-integrin ligation to endothelial counter ligands. We conclude that Pyk2 is activated by beta(2)-integrin adhesion and is a required signal for eosinophil spreading and subsequent chemotactic migration.
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PMID:Proline-rich tyrosine kinase 2 regulates spreading and migration of eosinophils after beta2-integrin adhesion. 1836 25

In the present study, Brucella melitensis biovar Abortus 2308 and Brucella abortus 3196 biotype 5 reference strains, which are susceptible to fluoroquinolones, became in vitro-resistant to fluoroquinolones by culture in trypticase soy agar. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes of the two reference strains were analysed by polymerase chain reaction sequencing analysis to obtain the wild-type sequence. These sequences were then compared with the corresponding sequences of four in vitro-selected fluoroquinolone-resistant mutants to characterise mutations associated with resistance. Sequencing of the ofloxacin-selected resistant mutant 2308 revealed a transition of GAT to AAT (corresponding to position 87 of Escherichia coli gyrA), leading to substitution of Asp91-->Asn, whilst at the same position the ciprofloxacin-selected resistant mutant 2308 revealed a transition of GAT to TAT (corresponding to the same position of E. coli as above), leading to substitution of Asp91-->Tyr. The ofloxacin-selected resistant mutant 3196 had a transition of GCT to GTT, generating an amino acid change of Ala87-->Val. Amino acid changes were detected in the portion of the Brucella gyrA gene (Ala71 to Gln110) corresponding to the E. coli gyrA QRDR region (Ala67 to Gln110). Amino acid changes were also detected in Ser83, corresponding to the region where fluoroquinolone-associated amino acid changes are most commonly found in other bacterial species.
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PMID:In vitro-selected resistance to fluoroquinolones in two Brucella strains associated with mutational changes in gyrA. 1858

Pannexin 1 (Panx1), an ortholog to invertebrate innexin gap junctions, has recently been proposed to be the pore induced by P2X(7) receptor (P2X(7)R) activation. We explored the pharmacological action of compounds known to block gap junctions on Panx1 channels activated by the P2X(7)R and the mechanisms involved in the interaction between these two proteins. Whole cell recordings revealed distinct P2X(7)R and Panx1 currents in response to agonists. Activation of Panx1 currents following P2X(7)R stimulation or by membrane depolarization was blocked by Panx1 small-interfering RNA (siRNA) and with mefloquine > carbenoxolone > flufenamic acid. Incubation of cells with KN-62, a P2X(7)R antagonist, prevented current activation by 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP). Membrane permeabilization to dye induced by BzATP was also prevented by Panx1 siRNA and by carbenoxolone and mefloquine. Membrane permeant (TAT-P2X(7)) peptides, provided evidence that the Src homology 3 death domain of the COOH-terminus of the P2X(7)R is involved in the initial steps of the signal transduction events leading to Panx1 activation and that a Src tyrosine kinase is likely involved in this process. Competition assays indicated that 20 microM TAT-P2X(7) peptide caused 50% reduction in Src binding to the P2X(7)R complex. Src tyrosine phosphorylation following BzATP stimulation was reduced by KN-62, TAT-P2X(7) peptide, and by the Src tyrosine inhibitor PP2 and these compounds prevented both large-conductance Panx1 currents and membrane permeabilization. These results together with the lack Panx1 tyrosine phosphorylation in response to P2X(7)R stimulation indicate the involvement of an additional molecule in the tyrosine kinase signal transduction pathway mediating Panx1 activation through the P2X(7)R.
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PMID:P2X7 receptor-Pannexin1 complex: pharmacology and signaling. 1859 11

Although it is well established that AMPA receptor (AMPAR) trafficking is a central event in several forms of synaptic plasticity, the mechanisms that regulate the surface expression of AMPARs are poorly understood. Previous work has shown that striatal-enriched protein tyrosine phosphatase (STEP) mediates NMDAR endocytosis. This protein tyrosine phosphatase is enriched in the synapses of the striatum, hippocampus, cerebral cortex, and other brain regions. In the present investigation, we have explored whether STEP also regulates AMPAR internalization. We found that (RS)-3,5-dihydroxyphenylglycine (DHPG) stimulation triggered a dose-dependent increase in STEP translation in hippocampal slices and synaptoneurosomes, a process that requires stimulation of mGluR5 (metabotropic glutamate receptor 5) and activation of mitogen-activated protein kinases and phosphoinositide-3 kinase pathways. DHPG-induced AMPAR internalization and tyrosine dephosphorylation of GluR2 (glutamate receptor 2) was blocked by a substrate-trapping TAT-STEP [C/S] protein in hippocampal slices and cultures. Moreover, DHPG-triggered AMPAR internalization was abolished in STEP knock-out mice and restored after replacement of wild-type STEP. These results suggest a role for STEP in the regulation of AMPAR trafficking.
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PMID:The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation. 1892 32

We describe the identification of a new DRB1*14 allele, DRB1*1461, found in a Chinese individual. The novel allele has been identified in routine polymerase chain reaction-sequence-specific oligonucleotide and sequence-based typing. The nucleotide sequence of DRB1*1461 is identical to DRB1*1404 except for a single substitution in codon 16 (TAT-->CAT), leading to a change from Tyr to His.
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PMID:Identification of a novel HLA-DRB allele, HLA-DRB1*1461. 1900 Jan 32

Complete androgen insensitivity syndrome is an X-linked inherited disorder caused by mutations in the androgen receptor (AR) gene. Using polymerase chain reaction single-strand DNA conformational polymorphism and DNA sequencing, we identified a novel nonsense mutation in exon 1 of the AR gene in 2 Iranian brothers with complete androgen insensitivity syndrome. Despite a normal 46,XY karyotype, testes, and normal to elevated plasma levels of testosterone, they were born with female external genitalia and phenotype. This new mutation, a T-to-A transversion in exon 1, causes amino acid change of tyrosine (TAT) to ochre stop codon (TAA) at position 514 of the AR polypeptide. The Y514X mutation is located in a region that is normally important for the formation and function of the hormone receptor complex. We conclude that the novel Y514X mutation in the androgen receptor is the cause of complete androgen insensitivity syndrome in this family.
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PMID:Identification of a critical novel mutation in the exon 1 of androgen receptor gene in 2 brothers with complete androgen insensitivity syndrome. 1902 43

We report an early detection of cancer in a child with Li-Fraumeni syndrome. The proband was a 3-year-old male with a primitive mesenchymal tumor. Genetic analysis showed a germline TP53 mutation in codon 220 exon 6, which changed TAT --> TGT and resulted in a tyrosine-to-cysteine amino acid substitution (Tyr220Cys). The younger sister at risk was followed, and an asymptomatic adrenal cortical carcinoma was detected 3 years later. The report highlights the importance of genetic counseling and provides an example of early detection of cancers in childhood LFS carriers.
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PMID:Early detection of adrenocortical carcinoma in a child with Li-Fraumeni syndrome. 1910 93

Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bidirectional signaling through cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, and we previously observed that signaling through the C-terminus of ephrin-B1 mediates the migration and invasion of cells, and is involved in the promotion of carcinomatous peritonitis in vivo. Here we show that the intracellular introduction of a synthetic peptide derived from ephrin-B1 C-terminus blocks ephrin-B1 mediated signaling in scirrhous gastric cancer cells. Treatment of cancer cells with a fusion peptide consisting of HIV-TAT and amino acids 331-346 of ephrin-B1 (PTD-EFNB1-C) suppressed the activation of RhoA, mediated by the association of ephrin-B1 with an adaptor protein Dishevelled, and also inhibited extracellular secretion of metalloproteinase. Moreover, injection of PTD-EFNB1-C peptide into the peritoneal cavity of nude mice suppressed carcinomatous peritonitis of intraperitoneally transplanted scirrhous gastric cancer cells. These results indicate the possible application of ephrin-B1 C-terminal peptide to develop novel protein therapy for scirrhous gastric carcinoma, especially in the stage of tumor progression, including peritoneal dissemination.
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PMID:Suppression of gastric cancer dissemination by ephrin-B1-derived peptide. 1980 21

ABSTRACT Wheat head blight caused by Gibberella zeae (anamorph: Fusarium graminearum) is a threat to food safety in China because of mycotoxin contamination of the harvested grain, the frequent occurrence of the disease, and the failure of chemical control in some areas due to benzimidazole resistance in the pathogen population. The molecular resistance mechanism, however, of G. zeae to benzimidazole fungicides (especially carbendazim; active ingredient: methyl benzimidazol-2-yl carbamate [MBC]) is poorly understood. DNA sequences of a beta-tubulin gene (beta(2)tub) (GenBank access number FG06611.1) in G. zeae were analyzed. Mutations in beta(2)tub in moderately resistant strains (MBC(MR)) included TTT (Phe)-->TAT (Tyr) at codon 167 or TTC (Phe)-->TAC (Tyr) at codon 200. A highly resistant strain (MBC(HR)) had two point mutations, one at codon 73, CAG (Gln)-->CGG (Arg), and the other at codon 198, GAG (Glu)-->CTG (Leu). To confirm that mutations in the beta(2)tub confer resistance to benzimidazole fungicides, the entire beta(2)tub locus was deleted from MBC(MR) and MBC(HR) strains of G. zeae. The resulting Deltabeta(2)tub mutants from both MBC(MR) and MBC(HR) strains grew normally on MBC-free potato dextrose agar medium and were supersensitive to MBC. Complementation of the Deltabeta(2)tub mutants by transformation with a copy of the intact beta(2)tub locus from their parent strains exhibited less resistance than the original strains, and complementation of the Deltabeta(2)tub mutants by transformation with a copy of the intact beta(2)tub locus from sensitive strains restored MBC sensitivity. The results indicated that the mutations in the beta(2)tub gene conferred resistance of G. zeae to benzimidazole fungicides and this gene can be used as a genetic marker in G. zeae.
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PMID:Mutations in a beta-tubulin confer resistance of Gibberella zeae to benzimidazole fungicides. 1990 7

A number of cell-penetrating peptides (CPPs) have been reported, but their transduction efficiencies are too low to be used as intracellular carriers for therapeutic purposes. We conducted a comprehensive search to find novel CPPs using an in vitro virus (IVV) library, which presented random peptides consisting of 15 amino acids (diversity of the library was >10(12)). We found 9 kinds of novel CPPs with an intracellular translocation efficiency higher than that of the TAT peptide (YGRKKKRRQRRR). Interestingly, one of the novel CPPs, No. 14 (KLWMRWYSPTTRRYG), showed a dramatic improvement in translocation activity relative to the TAT peptide in CHO cells (>10-fold efficiency in 50 microM). As the intracellular translocation efficiency of No. 14 was increased by substitution Arg for Lys1 (14-1), we carried out alanine scanning on the basis of 14-1 to determine important amino acids for the intracellular translocation. The Ala substitution analysis showed that both Arg and Trp residues were important for the cell-penetrating activity and that their contribution was in the order Trp3<Arg12<Arg1<Arg5, Arg13<Trp6. Moreover, it was possible to substitute two Trp with other bulky amino acids such as Ile or Tyr. In this study, we showed that novel CPPs could be acquired by screening random peptides and modifying some amino acids could increase their cell-penetrating activity.
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PMID:Isolation of novel cell-penetrating peptides from a random peptide library using in vitro virus and their modifications. 1995


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