MAPKAPK2 (Phospho-Thr334) ELISA Kit

Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Cell senescence is a complex process that can be triggered by multiple challenges. Recently it has been observed that the composition of the secretory phenotype or SASP depends on the insult that triggers cell senescence. Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while silencing the Nrf2 gene induces premature senescence. We have found that rapamycin activates the Nrf2 pathway to regulate cell cycle arrest, but not the production of SASP, which is regulated by a different pathway, probably involving the inhibition of MAPKAPK2. (C) 2017 Elsevier Inc. All rights reserved.

Upon encountering physiological cues associated with damaged or inflamed endothelium, blood platelets set forth intracellular responses to ultimately support hemostatic plug formation and vascular repair. To gain insights into the molecular events underlying platelet function, we used a combination of interactome, pathway analysis, and other systems biology tools to analyze associations among proteins functionally modified by reversible phosphorylation upon platelet activation. While an interaction analysis mapped out a relative organization of intracellular mediators in platelet signaling, pathway analysis revealed directional signaling relations around protein kinase C (PKC) isoforms and mitogen-activated protein kinases (MAPKs) associated with platelet cytoskeletal dynamics, inflammatory responses, and hemostatic function. Pathway and causality analysis further suggested that platelets activate a specific p38-MK2 axis to phosphorylate RTN4 (reticulon-4, also known as Nogo), a Bcl-xl sequestration protein and critical regulator of endoplasmic reticulum (ER) physiology. In vitro, we find that platelets drive a p38-MK2-RTN4-Bcl-xl pathway associated with the regulation of the ER and platelet phosphatidylserine exposure. Together, our results support the use of pathway tools in the analysis of omics data sets as a means to help generate novel, mechanistic, and testable hypotheses for platelet studies while uncovering RTN4 as a putative regulator of platelet cell physiological responses.