As shown in Figure 3h, Wnt3a increased both Numb and NumbL expression at the transcriptional and protein levels.
As shown in Figure 3b, the co-transfection of CA-PKC θ results in a marked increase of cytosolic Numb and a decrease of nuclear Numb.
Conversely, increased levels of Numb in the Isl1+ Nkx2.5− CPCs promoted their proliferation.
Conversely, in the absence of pre-TCR, the treatment with phorbol ester (phorbol-12-myristate-13-acetate (PMA)), a potent activator of PKC in eukaryotic cells, promotes an increase of phospho-Numb levels that correlates with an increase of the PKC θ activity.
Accordingly, an opposite effect was observed when PKC θ activity was mimicked in the absence of pre-TCR, by using PMA: while cytosolic Numb levels increase, nuclear Numb levels decrease markedly after PMA treatment of pre-TCR negative SCIET27 cells.
Although with extreme levels of depression there is less crying and more emotional numbing, an increase in crying could be a sign of depression, Bylsma says.
Pharmacologic treatments, which decrease or increase PKC θ activity, changed Numb localization pattern and impact in the half-life of Numb; when SCB29 cells were treated with Rottlerin in the presence of CHX, there was a significant decline in the half-life of Numb protein.
Notably, Numb total levels increased after PMA treatment, suggesting that p53 stabilization was dependent on nuclear Numb levels but not on total Numb levels.
β-Catenin activation increases levels of Notch inhibitors Numb and NumbL leading to the induction of pro-neuronal gene expression.
Consistently, thymocytes from pT α−/− mice showed low basal phosphorylation levels of Numb that were increased in the presence of PMA.
