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Review
. 2024 May 4;14(5):556.
doi: 10.3390/biom14050556.

Bone and Extracellular Signal-Related Kinase 5 (ERK5)

Lei Wen  1   2   3 , Zirui Liu  1   2 , Libo Zhou  1   2 , Zhongcheng Liu  1   2 , Qingda Li  1   2 , Bin Geng  1   2 , Yayi Xia  1   2
Affiliations
Review

Bone and Extracellular Signal-Related Kinase 5 (ERK5)

Lei Wen et al. Biomolecules. .

Abstract

Bones are vital for anchoring muscles, tendons, and ligaments, serving as a fundamental element of the human skeletal structure. However, our understanding of bone development mechanisms and the maintenance of bone homeostasis is still limited. Extracellular signal-related kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, plays a critical role in the pathogenesis and progression of various diseases, especially neoplasms. Recent studies have highlighted ERK5's significant role in both bone development and bone-associated pathologies. This review offers a detailed examination of the latest research on ERK5 in different tissues and diseases, with a particular focus on its implications for bone health. It also examines therapeutic strategies and future research avenues targeting ERK5.

Keywords: ERK5; bone; cancer; homeostasis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ERK5 localization and activation. In the resting state, ERK5 is present in the cytoplasm, and molecular interactions between the N-terminus and C-terminus of ERK5 place it in a folded state, which reduces the activity of the nuclear localization signal (NLS) or generates a nuclear export signal (NES) and binds to the cytoplasmic anchoring protein Hsp90. When the ERK5 TEY motif is phosphorylated and activated, the C-terminal half of ERK5 can autophosphorylate, inducing an unfolded state and dissociation from Hsp90, leading to NLS exposure and ERK5 nuclear translocation. When ERK5 is dephosphorylated in the nucleus, it resumes its folding transition and translocates to the cytoplasm. PR1: proline-rich 1; PR2: proline-rich 2.
Figure 2
Figure 2
The role of ERK5 in maintaining bone homeostasis.
See this image and copyright information in PMC

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