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)

Due to its pivotal role in the growth factor-mediated tumour cell migration, the adaptor protein phospholipase C-gamma1 (PLC-gamma1) is an appropriate target to block ultimately the spreading of EGFR/c-erbB-2-positive tumour cells, thereby minimising metastasis formation. Here, we present an approach to block PLC-gamma1 activity by using protein-based PLC-gamma1 inhibitors consisting of PLC-gamma1 SH2 domains, which were fused to the TAT-transduction domain to ensure a high protein transduction efficiency. Two proteins were generated containing one PLC-gamma1-SH2-domain (PS1-TAT) or two PLC-gamma1-SH2 domains (PS2-TAT). PS2-TAT treatment of the EGFR/c-erbB-2-positive cell line MDA-HER2 resulted in a reduction of the EGF-mediated PLC-gamma1 tyrosine phosphorylation of about 30%, concomitant with a complete abrogation of the EGF-driven calcium influx. In addition to this, long-term PS2-TAT treatment both reduces the EGF-mediated migration of about 75% combined with a markedly decreased time locomotion of single MDA-HER2 cells as well as decreases the proliferation of MDA-HER2 cells by about 50%. Due to its antitumoral capacity on EGFR/c-erbB-2-positive breast cancer cells, we conclude from our results that the protein-based PLC-gamma1 inhibitor PS2-TAT may be a means for novel adjuvant antitumour strategies to minimise metastasis formation because of the blockade of cell migration and proliferation.
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PMID:Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells. 1471 Feb 34

Human immunodeficiency virus TAT plays an important role in the disregulation of cytokine production associated with the neurological disorders that follow HIV infection. IL-1beta is one of the important inflammatory cytokines secreted by immune-activated monocytes/macrophages. Previous reports have shown that extracellular TAT stimulates IL-1beta expression in monocytes/macrophages. However, little is known about the mechanisms and possible TAT-responsive elements within the IL-1beta promoter. The present study shows that TAT increases the production of IL-1beta in human monocytes; PLC-PKC pathway-dependent phosphorylation of p44/42 and JNK MAP kinases participates partially in IL-1beta induction by TAT; specific C/EBP and NF-kappaB transcription factor binding elements within the IL-1beta promoter are involved in TAT regulation of IL-1beta production. This study identifies a signaling mechanism for HIV-1-induced IL-1beta production in human monocytes that may be involved in the neuropathogenesis of HIV-associated dementia.
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PMID:Mechanism of HIV-1-TAT induction of interleukin-1beta from human monocytes: Involvement of the phospholipase C/protein kinase C signaling cascade. 2033 59