MAPKAPK2

Case study 1: Jose B Saenz, 2010

Mounting evidence suggests that Shiga toxin (STx) activates stress response pathways in susceptible cells and has implicated the p38 mitogen-activated protein kinase (MAPK) pathway. More importantly, some of the pathology associated with haemolytic uremic syndrome (HUS) is believed to be a result of a STx-induced inflammatory response. However, the mechanism is not clear.

From a siRNA screen of the human kinome adapted to a high-throughput format, the researchers found that knock-down of MK2 protected against Shiga toxicity. Further characterization of the in vitro role of MK2 revealed that STx activates the p38-MK2 stress response pathway in both p38- and MK2-dependent manners in two distinct cell lines. MK2 activation was specific to damage to the ribosome by an enzymatically active toxin and did not result from translational inhibition per se. These findings suggest that MK2 inhibition might play a valuable role in decreasing the immuopathological component of STx-mediated disease.

Fig1. STx1 specifically induces activation of the p38-MK2 pathway in both HeLa and HMVEC in time- and dose-dependent manners.

Fig2. STx activation of the p38-MK2 pathway is dependent on MK2 activity. Overexpression of catalytically inactive MK2 (MK2-DN) eliminates STx1-induced Hsp27 phosphorylation.

Case study 2: Nicolás Herranz, 2015

Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1.

In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses.

Fig3. The association of MAPKAPK2 mRNA with polysomes significantly decreases upon acute mTOR inhibition.

Fig4. mTOR regulates the SASP by controlling MAPKAPK2 translation. The expression of de novo synthesised proteins was analyzed by immunoblot.

Fig1. MK2 regulates nuclear factor kappa B (NF-κB) transcription by altering the location of p38 MAPK. (Deri Morgan, 2022)

Fig2. Pathological consequences of the activation of the PKR/p38/RIPK1 pathway during neuronal stress and Alzheimer's disease (AD). (Jacques Hugon, 2021)

MAPKAPK2 involved in several pathways and played different roles in them. We selected most pathways MAPKAPK2 participated on our site, such as MAPK signaling pathway, VEGF signaling pathway, Neurotrophin signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with MAPKAPK2 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

MAPKAPK2 has several biochemical functions, for example, ATP binding, calcium-dependent protein serine/threonine kinase activity, calmodulin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by MAPKAPK2 itself. We selected most functions MAPKAPK2 had, and list some proteins which have the same functions with MAPKAPK2. You can find most of the proteins on our site.

MAPKAPK2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with MAPKAPK2 here. Most of them are supplied by our site. Hope this information will be useful for your research of MAPKAPK2.

MAPK14; HSPB1; HSF1; STAT3; saicar; ALOX5; PKM