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

The 130 kd transforming protein of Fujinami sarcoma virus (FSV P130gag -fps) possesses a tyrosine-specific protein kinase activity and is itself phosphorylated at several tyrosine and serine residues in FSV-transformed cells. We have used oligonucleotide-directed mutagenesis of the FSV genome to change the TAT codon for tyrosine (1073), the major site of P130gag -fps phosphorylation, to a TTT codon for phenylalanine that cannot be phosphorylated. This mutant FSV induces the transformation of rat-2 cells but with a long latent period as compared with wild-type FSV. The P130gag -fps protein encoded by the mutant retains the ability to phosphorylate tyrosine, but is five times less active as a kinase in vitro than wild-type FSV P130gag -fps. These data indicate that tyrosine phosphorylation stimulates the biochemical and biological activities of FSV P130gag -fps, and they set a precedent for the ability of this amino acid modification to modulate protein function.
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PMID:Mutagenesis of Fujinami sarcoma virus: evidence that tyrosine phosphorylation of P130gag-fps modulates its biological activity. 632 76

Cancer patients are subjected to increased systemic risk of thrombotic events and may therefore be at higher risk of even local thrombosis compromising the outcome of reconstructive microsurgery. Coagulation and fibrinolysis activities were studied serially during and after reconstructive microsurgery in seven patients with oropharyngeal cancer or sarcoma in the extremities. A preoperative hypercoagulable state was found in four patients (elevated fibrinogen, TAT, F1+2, or D-dimer); two of these patients also had a local thrombotic event. In all patients, the plasma markers generally varied perioperatively: fibrinogen decreased, whereas TAT and subsequently D-dimer increased at the end of the operation. However, tPA and PAI-1 remained unaltered, except in the patients with thrombosis in whom PAI-1 activity increased progressively during the operation. F1+2 was also clearly elevated in these two patients at the time of thrombosis. Preoperative assessment of hypercoagulability for this group of patients could be helpful in targeting meticulous antithrombotic protection.
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PMID:Activation of coagulation and fibrinolysis during reconstructive microsurgery in patients with cancer. 1149 94

Cortical spreading depression (CSD) is a propagating wave of depolarization followed by depression of cortical activity. CSD triggers neuroinflammation via the pannexin-1 (Panx1) channel opening, which may eventually cause migraine headaches. However, the regulatory mechanism of Panx1 is unknown. This study investigates whether sarcoma family kinases (SFK) are involved in transmitting CSD-induced Panx1 activation, which is mediated by the NR2A-containing N-methyl-D-aspartate receptor. CSD was induced by topical application of K+ to cerebral cortices of rats and mouse brain slices. SFK inhibitor, PP2, or NR2A-receptor antagonist, NVP-AAM077, was perfused into contralateral cerebral ventricles (i.c.v.) of rats prior to CSD induction. Co-immunoprecipitation and Western blot were used for detecting protein interactions, and histofluorescence for addressing Panx1 activation. The results demonstrated that PP2 attenuated CSD-induced Panx1 activation in rat ipsilateral cortices. Cortical susceptibility to CSD was reduced by PP2 in rats and by TAT-Panx308 that disrupts SFK-Panx1 interaction in mouse brain slices. Furthermore, CSD promoted activated SFK coupling with Panx1 in rat ipsilateral cortices. Moreover, inhibition of NR2A by NVP-AAM077 reduced elevation of ipsilateral SFK-Panx1 interaction, Panx1 activation induced by CSD and cortical susceptibility to CSD in rats. These data suggest NR2A-regulated, SFK-dependent Panx1 activity plays an important role in migraine aura pathogenesis.
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PMID:Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression is Mediated by NR2A-Containing Receptors. 3207 42