Mitogen- and stress-activated protein kinase 2 (MSK2) (MSK2)

Mitogen- and stress-activated protein kinase 2 (MSK2), also known as RPS6KA4, is a nuclear serine/threonine kinase belonging to the ribosomal S6 kinase (RSK) family [1.2.2, 1.2.3]. It is activated downstream of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) pathways in response to growth factors, cytokines, and environmental stresses such as UV radiation [1.2.1, 1.4.3]. MSK2 functions as a key regulator of gene expression by phosphorylating transcription factors, including CREB, ATF1, and the p65 subunit of NF-kappaB, as well as chromatin proteins like Histone H3 [1.2.2, 1.4.1, 1.4.4]. In disease contexts, MSK2 is implicated in cancer progression, where it can inhibit p53-mediated apoptosis in a kinase-independent manner and promote cell survival and transformation [1.2.1, 1.3.2]. It also plays a significant role in inflammation, regulating the production of both pro-inflammatory and anti-inflammatory cytokines, such as IL-10 [1.3.4, 1.4.1]. Therapeutic targeting of MSK2 is being explored for inflammatory diseases and various cancers, with small-molecule inhibitors like SB-747651A and dimethyl fumarate being used to modulate its activity in preclinical studies [1.2.2, 1.2.5, 1.3.3].

Other names

RPS6KA4Ribosomal protein S6 kinase alpha-4RSK-BS6K-alpha-490 kDa ribosomal protein S6 kinase 4Nuclear mitogen- and stress-activated protein kinase 2Ribosomal protein kinase B

Inhibition of kinase activity through ATP-competitive binding to the catalytic domains or covalent modification of regulatory residues.