ERK8

ERK8, also known as MAPK15, is an atypical mitogen-activated protein kinase that regulates autophagy, ciliogenesis, protein trafficking, and genome integrity through mechanisms that differ from those of classical ERK family members^[1]^[2]. Mechanistically, ERK8 participates in the autophagic machinery by interacting with LC3 and GABARAP family proteins and by regulating ULK1 complex activity, thereby promoting early stages of autophagosome biogenesis and cellular stress adaptation^[3]^[4]. In addition to its role in autophagy, ERK8 functions as a chromatin-associated kinase that preserves genomic stability by preventing HDM2-mediated degradation of proliferating cell nuclear antigen (PCNA), a key factor required for DNA replication and DNA damage protection^[5]. Disease-related studies have linked MAPK15 dysregulation to multiple cancer models, including male germ cell tumors, ovarian cancer, gastric cancer, and lung adenocarcinoma, where elevated MAPK15 expression has been associated with tumor cell proliferation, migration, or metastatic behavior^[6]^[7]. Compared with the canonical ERK1/2 isoforms that primarily operate within the Ras-Raf-MEK-ERK signaling cascade, ERK8 is classified as an atypical MAP kinase and exhibits distinct regulatory mechanisms and substrate interactions, supporting specialized functions in autophagy, genome maintenance, and ciliary biology^[1]^[2]. For experimental applications, structural characterization of the ERK8 kinase domain has provided a framework for target validation and future development of selective pharmacological modulators for mechanistic studies^[8].

References:

[1]. Uniprotkb.

[2]. ERK8 gene information from NCBI.

[3]. Colecchia D, et al. MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. Autophagy. 2012 Dec;8(12):1724-40. [Content Brief]

[4]. Colecchia D, et al. MAPK15 is part of the ULK complex and controls its activity to regulate early phases of the autophagic process. J Biol Chem. 2018 Oct 12;293(41):15962-15976. [Content Brief]

[5]. Groehler AL, et al. A chromatin-bound kinase, ERK8, protects genomic integrity by inhibiting HDM2-mediated degradation of the DNA clamp PCNA. J Cell Biol. 2010 Aug 23;190(4):575-86. [Content Brief]

[6]. Yu FY, et al. The Atypical MAP Kinase MAPK15 Is Required for Lung Adenocarcinoma Metastasis via Its Interaction with NF-κB p50 Subunit and Transcriptional Regulation of Prostaglandin E2 Receptor EP3 Subtype. Cancers (Basel). 2023 Feb 22;15(5):1398. [Content Brief]

ERK8 Inhibitor (1)

ERK8 Related Products (1):

By Type:	Selective (1)

Cat. No.	Product Name	Effect	Purity

HY-135906

CK2/ERK8-IN-1	Inhibitor	99.0%
CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (K_i of 0.25 µM) and ERK8 (MAPK15, ERK7) inhibitor with IC₅₀s of 0.50 μM. CK2/ERK8-IN-1 also binds to PIM1, HIPK2 (homeodomain-interacting protein kinase 2), and DYRK1A with K_is of 8.65 µM, 15.25 µM, and 11.9 µM, respectively. CK2/ERK8-IN-1 has pro-apoptotic efficacy.

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