MAPK1

MAPK1 Background

Mitogen-activated protein kinase 1 is a protein in humans that is encoded by the MAPK1 gene ^[1]. MAPK1 is also known as p42MAPK or ERK2. MAPK1 is a serine/threonine kinase that acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the two MAPKs that play an important role in the MAPK/ERK cascade. The MAPK pathway consists of protein kinases that are activated in sequential order and couples extracellular signals to intracellular appropriate responses, including cell proliferation, inflammatory responses, development, differentiation, and apoptosis ^[2][3]. The MAPK/ERK cascade also plays a role in the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating some transcription factors. The previous study demonstrated that ERK2 downregulation by specific siRNAs could promote higher chemosensitivity compared with an ERK1 knockdown in human hepatocellular carcinoma cell line ^[4]. Additionally, ERK2 knockdown resulted in a higher overexpression of ERK1 than that of ERK2 in ERK1 knockdown, suggesting the crucial role of ERK2 in cancer. Furthermore, it has been shown that ERK1-mutant mouse fibroblasts sustain ERK2 activation, resulting in c-fos and zif-268 overexpression and consequent elevated cell proliferation. These data indicated that ERK1 elimination can facilitate ERK2 signaling ^[5]. For example, the ERK1-null mouse is viable and fertile whereas ERK2 knockout is embryonic lethal ^[6][7]. Accordingly, ERK2 plays an important role in embryonic development ^[8].

[1] Owaki H, Makar R, et al. Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs [J]. Biochem. Biophys. Res. Commun. 1992, 182 (3): 1416-22.
[2] Widmann C, Gibson S, et al. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human [J]. Physiol Rev. 1999 Jan; 79(1):143-80.
[3] Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells [J]. Cell Res. 2002 Mar; 12(1):9-18.
[4] Mehdizadeh A, Somi MH, et al. Liposome-mediated RNA interference delivery against Erk1 and Erk2 does not equally promote chemosensitivity in human hepatocellular carcinoma cell line HepG2 [J]. Artif Cells Nanomed Biotechnol. 2017 Dec; 45(8):1612-1619.
[5] Vantaggiato C, Formentini I, et al. ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially [J]. J Biol. 2006; 5(5):14.
[6] Nekrasova T, Shive C, et al. ERK1-deficient mice show normal T cell effector function and are highly susceptible to experimental autoimmune encephalomyelitis [J]. J Immunol. 2005 Aug 15; 175(4):2374-80.
[7] Yao Y, Li W, et al. Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation [J]. Proc Natl Acad Sci U S A. 2003 Oct 28; 100(22):12759-64.
[8] Newbern J, Zhong J, et al. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development [J]. Proc Natl Acad Sci U S A. 2008 Nov 4; 105(44):17115-20.