Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infusion of prostacyclin (PGI2) reportedly attenuates renal ischemic injury in the dog and the rat. In the dog, PGI2 is a potent renal vasodilator; in the rat a direct action on the renal vasculature is not always apparent. To determine whether or not the protective effect of PGI2 on postischemic ARF was hemodynamically mediated, studies were performed in uninephrectomized Sprague-Dawley rats before and after a 40 minute period of complete renal artery occlusion. In response to the preischemic infusion of PGI2 for 30 minutes at 160 ng/kg body wt/min i.v. (N = 7), MAP and RBF fell to 86 +/- 7% (P less than 0.0001) and 84 +/- 9% (P less than 0.05) of baseline values, respectively. RVR initially declined to 81 +/- 9% of baseline values (P less than 0.025) but returned to 102 +/- 13% of baseline values prior to the period of ischemia. Following the period of ischemia, reflow of blood in the rats receiving PGI2 was delayed when compared to rats not receiving PGI2 (N = 7). RBF returned to only 76 +/- 19% of the initial values in PGI2-treated rats (P less than 0.01) but to 90 +/- 12% of the initial values in rats receiving buffer alone (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of prostacyclin on postischemic acute renal failure in the rat. 332 94

Binding of Src family kinases to membrane-associated polyoma virus middle T-antigen (PyMT) can result in the phosphorylation of PyMT tyrosine 250, which serves as a docking site for the binding of Shc and subsequent activation of the Raf-MEK-ERK (MAP) kinase cascade. In a screen for PyMT variants that could not activate the ARF tumor suppressor, we isolated a cytoplasmic nontransforming mutant (MTA) that encoded a C-terminal truncated form of the PyMT protein. Surprisingly, MTA was able to strongly activate the MAP kinase pathway in the absence of Src family kinase and Shc binding. Interestingly, the polyoma small T-antigen (PyST), which shares with MTA both partial amino acid sequence homology and cellular location, also activates the MAP kinase cascade. Activation of the MAP kinase cascade by both MTA and PyST has been demonstrated to be PP2A-dependent. Neither MTA nor PyST activate the phosphorylation of AKT. The SV40 small T-antigen, which is similar to PyST in containing a J domain and in binding to the PP2A AC dimer, does not activate the MAP kinase cascade, but does stimulate phosphorylation of AKT in a PP2A-dependent manner. These findings highlight a novel role of PP2A in stimulating the MAP kinase cascade and indicate that the similar polyoma and SV40 small T-antigens influence PP2A to activate discrete cellular signaling pathways involved in growth control.
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PMID:Polyoma and SV40 proteins differentially regulate PP2A to activate distinct cellular signaling pathways involved in growth control. 1715 97

ARF is a tumour suppressor activated by oncogenic stress, which stabilizes p53. Although p53 is a key component of the response to DNA damage, a similar function for ARF has not been ascribed. Here we show that primary mouse and human cells lacking the tumour suppressor BRCA2 accumulate DNA damage, which triggers checkpoint signalling and ARF activation. Furthermore, senescence induced by Brca2 deletion in primary mouse and human cells is reversed by the loss of ARF, a phenotype recapitulated in cells lacking RAD51. Surprisingly, ARF is not necessary for p53 accumulation per se but for altering the spectrum of genes activated by this transcription factor. Specifically, ARF enables p53 transcription of Dusp4 and Dusp7, which encode a pair of phosphatases known to inactivate the MAP kinases ERK1/2. Our results ascribe a previously unanticipated function to the ARF tumour suppressor in genome integrity, controlled by replicative stress and ATM/ATR-dependent checkpoint responses.
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PMID:ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets. 2416 89