Crosstalk between p38 MAPK and GR Signaling

Abstract

The p38 MAPK is a signaling pathway important for cells to respond to environmental and intracellular stress. Upon activation, the p38 kinase phosphorylates downstream effectors, which control the inflammatory response and coordinate fundamental cellular processes such as proliferation, apoptosis, and differentiation. Dysregulation of this signaling pathway has been linked to inflammatory diseases and cancer. Secretion of glucocorticoids (GCs) is a classical endocrine response to stress. The glucocorticoid receptor (GR) is the primary effector of GCs and plays an important role in the regulation of cell metabolism and immune response by influencing gene expression in response to hormone-dependent activation. Its ligands, the GCs or steroids, in natural or synthetic variation, are used as standard therapy for anti-inflammatory treatment, severe asthma, autoimmune diseases, and several types of cancer. Several years ago, the GR was identified as one of the downstream targets of p38, and, at the same time, it was shown that glucocorticoids could influence p38 signaling. In this review, we discuss the role of the crosstalk between the p38 and GR in the regulation of gene expression in response to steroids and comprehend the importance and potential of this interplay in future clinical applications.

Expression patterns of AMPK and genes associated with lipid metabolism in newly hatched chicks during the metabolic perturbation of fasting and refeeding

“…GR mediates most biological effects of glucocorticoids ( GCs ) ( Motavalli et al, 2021 ; Zeyen et al, 2022 ). After binding to GCs, GR is separated from its chaperone complex and translocated to the nucleus, where it regulates gene transcription by binding to GC response elements in the control region of the target gene ( Wang et al, 2012a ).…”

Intermittent Hypoxia on the Attenuation of Induced Nasal Allergy and Allergic Asthma by MAPK Signaling Pathway Downregulation in a Mice Animal Model

“…Also, CIH decreased the glucosteroid sensitivity by activating the p38 MAPK signaling pathway. Additionally, ERK and JNK phosphorylation and activation also can be affected after stimulation with glucosteroids, although the mechanism of this regulation is not fully elucidated [ 19 ]. Other studies have shown that CIH exposure led to the activation of the p38 MAPK pathway in the nervous system and vascular endothelium [ 8 ].…”

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

“…The p38 MAPK is an important signaling molecule, which responds to environmental and intracellular stress, and is related to cell proliferation, apoptosis, inflammation, metastasis, and angiogenesis (Figure 3 ). 68 , 69 …”

“…The p38 MAPK is an important signaling molecule, which responds to environmental and intracellular stress, and is related to cell proliferation, apoptosis, inflammation, metastasis, and angiogenesis (Figure 3). 68,69 There are eight drugs targeting the p38 MAPK family in the PKIDB or in FDA approved drugs 5 : acumapimod, dilmapimod, doramapimod, losmapimod, neflamapimod, pamapimod, ralimetinib, and talmapimod. These p38 MAPK inhibitors are often used in various inflammatory diseases.…”