The roles of MAPKs in disease

Abstract

MAP kinases transduce signals that are involved in a multitude of cellular pathways and functions in response to a variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identified in diseases ranging from cancer to inflammatory disease to obesity and diabetes. In many cell types, the MAPKs ERK1/2 are linked to cell proliferation. ERK1/2 are thought to play a role in some cancers, because mutations in Ras and B-Raf, which can activate the ERK1/2 cascade, are found in many human tumors. Abnormal ERK1/2 signaling has also been found in polycystic kidney disease, and serious developmental disorders such as cardio-facio-cutaneous syndrome arise from mutations in components of the ERK1/2 cascade. ERK1/2 are essential in well-differentiated cells and have been linked to long-term potentiation in neurons and in maintenance of epithelial polarity. Additionally, ERK1/2 are important for insulin gene transcription in pancreatic beta cells, which produce insulin in response to increases in circulating glucose to permit efficient glucose utilization and storage in the organism. Nutrients and hormones that induce or repress insulin secretion activate and/or inhibit ERK1/2 in a manner that reflects the secretory demand on beta cells. Disturbances in this and other regulatory pathways may result in the contribution of ERK1/2 to the etiology of certain human disorders.

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

“…The phosphorylation of ERK is associated with cell proliferation and cell migration through effects on cell-matrix contacts. 46 It was also reported to be found in Müller-glial cells after RD. 47 Taken together, our results suggest that extracellular HMGB1 from dying ocular cells might affect retinal cells through ERK phosphorylation and potentially serve to promote the formation of PVR, which is wound healing, but has a pathological meaning in the eye.…”

Inhibitor of the transcription factor NF-κB, DHMEQ, enhances the effect of paclitaxel on cells of anaplastic thyroid carcinoma in vitro and in vivo

“…It is known that Ras and associated signaling cascade is експериментальні роботи able to activate NF-κB, especially in tumor cells [21], but the reverse effect of factor on this cascade was studied insufficiently. One of possible mechanisms of this activation can be a release of protein kinase TLP2 from the complex, consisting of MAPK/p105-subunit of NF-κB/TLP2 [22].…”

Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2

“…It has been reported that Gi/o proteins, which are known to affect a variety of cellular functions, activate p-ERK1/2 and subsequent cell proliferation signals [10,32]. AA metabolites are also able to induce cell growth and have been strongly implicated in tumor development [38,39].…”

“…Activation of the MAPK cascade is necessary for cell growth and proliferation [10]. The MAPK family serves as a convergence point for intracellular signal transduction pathways (including coupling HBx cytoplasmic signaling to its gene expression program) and functions as a mediator of cel-lular responses to a variety of cellular stimuli [11,12].…”