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The extracellular signal-regulated kinase (ERK) pathway has been shown to be activated by physiological agonists in T cells and implicated in their proliferative response. The major mediators of this pathway are the dual specificity phosphatase (DUSP) family of proteins, which dephosphorylate and, in turn, activate the MAPKs (mitogen-activated protein kinases). The membrane phospholipid sphingosine-1-phosphate (S1P) appears to mediate the activity of these DUSP proteins, by stabilizing the phosphorylated state of the ERK. We have investigated the role of this pathway in regulating the transcriptional activity of the human interleukin-2 (hIL-2) promoter. The use of dominant-negative mutants of the small GTPases of the Ras superfamily and the MAPK kinase MEK1 identified the Raf-MEK-ERK pathway as being required for the induction of IL-2 production in T cells. Using this system, we have found that both Ras and Raf can stimulate the activity of the IL-2 promoter, and these effects appear to be mediated through the activation of ERK. By contrast, stimulation of the hIL-2 promoter by S1P was not inhibited by dominant-negative Ras or Raf, and S1P was able to stimulate IL-2 transcription in the absence of these Ras and Raf factors. The activity of the ERK pathway in the hIL-2 promoter was further investigated by assessing its sensitivity to known inhibitors. Inhibitory antibodies against MEK and ERK, as well as the use of the DUSP inhibitor, were able to suppress the activity of the IL-2 promoter, whereas, interestingly, the effect of S1P was unaffected by the DUSP inhibitor. These results suggest that the ERK pathway, but not the S1P pathway, is directly involved in the regulation of IL-2 transcription 8e68912320 Tweak Disk Free Download Tweak Disk uses the KEYMACRO utility and the following command-line parameters to work: /dbname=Disk%N.EXE /src=The%N-tweaker.exe /targ=TheMessage.TXT Tweak Disk is free and the source code is available if you need to customize it to your own needs. To obtain an inexpensive CD with Tweak Disk and KEYMACRO, contact Tweak Disk's author, Franklin Drover.Q: Accessing a function outside the scope I have this JavaScript code: myFunction(3); function myFunction(x){ console.log(x); } What I am asking is: What if I declare the function outside of the scope of the parent function? Does it still work? And how would it work? This doesn't work: var myFunction = function(x){ console.log(x); }; myFunction(3); A: I think this should work. 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