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Updated: May 10, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
Published on: June 30, 2019
Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases
1University of Tromsø Faculty of Health Sciences, Department of Medical Biology, Molecular Inflammation Research Group, N-9037 Tromsø, Norway. ugo.moens@uit.no
Abstract:
Mitogen-activated protein kinase (MAPK) pathways are important signal transduction pathways that control pivotal cellular processes including proliferation, differentiation, survival, apoptosis, gene regulation, and motility. MAPK pathways consist of a relay of consecutive phosphorylation events exerted by MAPK kinase kinases, MAPK kinases, and MAPKs. Conventional MAPKs are characterized by a conserved Thr-X-Tyr motif in the activation loop of the kinase domain, while atypical MAPKs lack this motif and do not seem to be organized into the classical three-tiered kinase cascade. One functional group of conventional and atypical MAPK substrates consists of protein kinases known as MAPK-activated protein kinases. Eleven mammalian MAPK-activated protein kinases have been identified, and they are divided into five subgroups: the ribosomal-S6-kinases RSK1-4, the MAPK-interacting kinases MNK1 and 2, the mitogen- and stress-activated kinases MSK1 and 2, the MAPK-activated protein kinases MK2 and 3, and the MAPK-activated protein kinase MK5 (also referred to as PRAK). MK5/PRAK is the only MAPK-activated protein kinase that is a substrate for both conventional and atypical MAPK, while all other MAPKAPKs are exclusively phosphorylated by conventional MAPKs. This review focuses on the structure, activation, substrates, functions, and possible implications of MK5/PRAK in malignant and nonmalignant diseases.
Insights
Mitogen-activated protein kinase (MAPK) pathways regulate cell functions. This review details MAPK-activated protein kinase 5 (MK5/PRAK), a unique kinase involved in both conventional and atypical MAPK signaling, and its disease implications.
Area of Science:
- Cellular Biology
- Molecular Biology
- Signal Transduction
Background:
- Mitogen-activated protein kinase (MAPK) pathways are crucial for cellular processes like proliferation, differentiation, and apoptosis.
- MAPK pathways involve a cascade of phosphorylation events mediated by MAPK kinase kinases, MAPK kinases, and MAPKs.
- MAPK-activated protein kinases (MAPKAPKs) are key substrates of MAPK pathways, with eleven identified mammalian forms.
Purpose of the Study:
- To review the structure, activation mechanisms, substrates, and functions of MAPK-activated protein kinase 5 (MK5/PRAK).
- To explore the role and implications of MK5/PRAK in both malignant and nonmalignant diseases.
- To highlight MK5/PRAK's unique position as a substrate for both conventional and atypical MAPKs.
Main Methods:
- Literature review of existing research on MK5/PRAK.
- Analysis of structural and functional data of MK5/PRAK.
- Synthesis of information regarding MK5/PRAK's involvement in disease pathogenesis.
Main Results:
- MK5/PRAK is the sole MAPKAPK phosphorylated by both conventional and atypical MAPKs.
- Other MAPKAPKs are exclusively phosphorylated by conventional MAPKs.
- MK5/PRAK has diverse substrates and functions, impacting cellular signaling.
Conclusions:
- MK5/PRAK represents a unique node in MAPK signaling networks.
- Understanding MK5/PRAK's role is critical for deciphering complex cellular processes.
- MK5/PRAK holds potential as a therapeutic target in various diseases.
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