LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies

Kavita Shah1, Mason Cook1

  • 1Department of Chemistry and Purdue University Center for Cancer Research, 560 Oval Drive, West Lafayette, IN, 47907, USA.

Cancer Letters
|May 4, 2023
PubMed

Insights

LIMK2 (LIM kinase 2) is a kinase involved in cell growth and development. This review explores its function beyond actin regulation, revealing new roles in diseases and potential as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • LIMK2 (LIM-domain interacting kinase 2) is a serine kinase regulating actin dynamics.
  • Emerging evidence links LIMK2 to human malignancies and neurodevelopmental disorders.
  • Targeting LIMK2 shows promise, but its regulatory mechanisms and substrate specificity are poorly understood.

Purpose of the Study:

  • To review the catalytic mechanism, substrate specificity, and upstream regulation of LIMK2.
  • To explore LIMK2's roles beyond actin dynamics.
  • To highlight novel substrates and their implications in human physiology and pathology.

Main Methods:

  • Literature review of existing studies on LIMK2.
  • Analysis of LIMK2's catalytic activity and substrate interactions.
  • Discussion of transcriptional, post-transcriptional, and post-translational regulation.

Main Results:

  • LIMK2 possesses unique catalytic properties and substrate specificity.
  • LIMK2 is regulated at multiple levels, influencing its activity.
  • New substrates, including tumor suppressors and oncogenes, have been identified, revealing non-actin-related functions.

Conclusions:

  • LIMK2's roles extend beyond actin regulation, involving diverse cellular processes.
  • Understanding LIMK2's complete substrate repertoire is crucial for elucidating its pathological functions.
  • LIMK2 represents a promising therapeutic target for 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...
5.7K
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...
3.7K
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...
2.4K
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...
13.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K