Rabbit Anti-Human MAPKAPK2 (Phospho-Thr222) polyclonal antibody

Glioblastomas are the deadliest type of brain cancer and are frequently associated with poor prognosis and a high degree of recurrence despite removal by surgical resection and treatment by chemo- and radio-therapy. Photodynamic therapy (PDT) is a treatment well known to induce mainly necrotic and apoptotic cell death in solid tumors. 5-Aminolevulinic acid (5-ALA)-based PDT was recently shown to sensitize human glioblastoma cells (LN-18) to a RIP3 (Receptor Interacting Protein 3)-dependent cell death which is counter-acted by activation of autophagy. These promising results led us to investigate the pathways involved in cell death and survival mechanisms occurring in glioblastoma following PDT. In the present study, we describe a new TSC2 (Tuberous Sclerosis 2) -dependent survival pathway implicating MK2 (MAPKAPK2) kinase and 14-3-3 proteins which conducts to the activation of a pro-survival autophagy. Moreover, we characterized a new RIP3/TSC2 complex where RIP3 is suggested to promote cell death by targeting TSC2-dependent survival pathway. These results highlight (i) a new role of TSC2 to protect glioblastoma against PDT-induced cell death and (ii) TSC2 and 14-3-3 as new RIP3 partners. (C) 2016 Published by Elsevier B.V.

We have identified a novel series of substituted N,N'-diarylurea p38 alpha inhibitors. The inhibitory activity of the target compounds against the enzyme p38 alpha, MAPKAPK2 in BHK cells, TNF-alpha release in LPS-stimulated THP-1 cells and p38 alpha binding experiments were tested. Among these compounds, 25a inhibited the p38 alpha enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 x 10(-8) and appears to be the most promising one in the series.