Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression

Abstract

Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family of signaling molecules. ERK is predominantly found in two forms, ERK1 (p44) and ERK2 (p42), respectively. There are also several atypical forms of ERK, including ERK3, ERK4, ERK5 and ERK7. The ERK1/2 signaling pathway has been implicated in many and diverse cellular events, including proliferation, growth, differentiation, cell migration, cell survival, metabolism and transcription. ERK1/2 is activated (i.e., phosphorylated) in the cytosol and subsequently translocated to the nucleus, where it activates transcription factors including, but not limited to, ETS, c-Jun, and Fos. It is not surprising that the ERK1/2 signaling cascade has been implicated in many pathological conditions, namely, cancer, arthritis, chronic inflammation, and osteoporosis. This narrative review examines many of the cellular events in which the ERK1/2 signaling cascade plays a critical role. It is anticipated that agents designed to inhibit ERK1/2 activation or p-ERK1/2 activity will be developed for the treatment of those diseases characterized by dysregulated gene expression through ERK1/2 activation.

A comparison of mRNA and circRNA expression between squamous cell carcinoma and adenocarcinoma of the lungs

“…Moreover, the functional enrichment analysis implied that EPHA7 was significantly enriched in the regulation of ERK1 and ERK2 cascade. ERK1 / ERK2 signaling cascades have been widely reported to serve vital roles in various diseases, such as cancer and chronic inflammation ( Lu and Malemud, 2019 ). Lim et al (2017) indicated that coumestrol (a novel chemotherapeutic agent) might play a therapeutic role in prostate cancer by mediating ERK1/2 signaling pathway.…”

DUSP6 protects murine podocytes from high glucose‑induced inflammation and apoptosis

“…DUSPs tightly mediate the spatiotemporal activity and inactivation of mitogen-activated protein kinases (MAPKs) ( 28 ). As members of the MAPK family, ERK1/2 are highly homologous and function in the same protein kinase cascade ( 29 ), which is involved in a variety of pathological conditions, including inflammation, oxidative stress and cell senescence ( 30 – 32 ). Therefore, the modulatory effect of DUSP6 on ERK1/2 was investigated.…”

Disulfides from the Brown Alga Dictyopteris membranacea Suppress M1 Macrophage Activation by Inducing AKT and Suppressing MAPK/ERK Signaling Pathways

“…MAPK signaling pathway regulates a number of cellular processes, such as cell proliferation, survival, apoptosis, and transcription, indicating that MAPK signaling cascade is essential for a number of cellular processes, including immunity and metabolism [ 22 ]. Deregulation of ERK 1/2 signaling has been implicated in several inflammatory pathologies, such as rheumatoid arthritis, psoriatic arthritis and inflammatory bowel diseases, e.g., Crohn’s disease [ 23 ]. In addition, the PI3K/AKT/mTOR signaling pathway is activated upon several receptor signals, such as insulin and cytokines mediating inflammatory and metabolic processes orchestrating the inflammatory response [ 4 ].…”