Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases

Ugo Moens1, Sergiy Kostenko

  • 1University of Tromsø Faculty of Health Sciences, Department of Medical Biology, Molecular Inflammation Research Group, N-9037 Tromsø, Norway. ugo.moens@uit.no

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.

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...