We know the mutations associated with developmental syndromes cause a modest activation of MEK activity compared with activating mutations in the activation segment.
Interestingly the choice between p53-induced senescence and quiescence, in a context of cell cycle blockade, would be mediated by the activity of the mTOR pathway and the strength of the p53 response: while p53 modest activation preserves mTOR activity and therefore results in senescence, strong p53 activation inhibits mTOR and result in quiescence [ 29- 31].
In the presence of glutamine and PII-UMP, addition of ATN6 provided modest activation of the AT activity.
Such a model would fit with the modest activation of core GEF activity seen on rabaptin binding.
AKB-4924 is a PHD inhibitor that results in modest activation of HIF-2α but robustly activates HIF-1α [23].
Western blot analyses of Jak3 and Stat3 phosphorylation of T-cell protein extracts showed strong activation of Jak3 and modest activation of Stat3 upon S100A4 treatment, whereas the S100A4 mutant protein did not activate the phosphorylation.
This could be consistent with modest activation of the renin-angiotensin-aldosterone system (RAS) [22],[22].
DTAB caused a very modest activation of RARα, RXRα, and RXRγ, and no significant activation of RXRβ at concentrations tested.
There was a modest activation of the MAPK pathway as determined by levels of phosphorylated Erk 1/2 in the paediatric high grade lines SF188 and UW479 as compared to KNS42 and the low grade lines (Res259, Res186).
Amongst the 12 identified "fix+" regulators, only one (MT016186), although weakly expressed, seems to have a nodulation-specific expression pattern while two are nodule-preferential (Table 4), but with a modest activation ratio.
While Tat was able to mediate only a modest activation of these pathways by itself, in the presence of cytokines, it potentiated a robust activation of these pathways as compared with the cytokines by themselves.
