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Review
. 2023 Oct 7;13(10):1490.
doi: 10.3390/biom13101490.

Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review

Luka Katic  1   2 , Anamarija Priscan  3
Affiliations
Review

Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review

Luka Katic et al. Biomolecules. .

Abstract

This review commemorates the 10-year anniversary of the discovery of physiological ligands Augα (Augmentor α; ALKAL2; Fam150b) and Augβ (Augmentor β; ALKAL1; Fam150a) for anaplastic lymphoma kinase (ALK) and leukocyte tyrosine kinase (LTK), previously considered orphan receptors. This manuscript provides an in-depth review of the biophysical and cellular properties of ALK family receptors and their roles in cancer, metabolism, pain, ophthalmology, pigmentation, central nervous system (CNS) function, and reproduction. ALK and LTK receptors are implicated in the development of numerous cancers, and targeted inhibition of their signaling pathways can offer therapeutic benefits. Additionally, ALK family receptors are involved in regulating body weight and metabolism, modulating pain signaling, and contributing to eye development and pigmentation. In the CNS, these receptors play a role in synapse modulation, neurogenesis, and various psychiatric pathologies. Lastly, ALK expression is linked to reproductive functions, with potential implications for patients undergoing ALK inhibitor therapy. Further research is needed to better understand the complex interactions of ALK family receptors and Aug ligands and to repurpose targeted therapy for a wide range of human diseases.

Keywords: ALK; ALK inhibitor side effects; Augmentor α; Augmentor β; LTK; central nervous system biomolecules; pain modulation pathways; receptor tyrosine kinases; signaling pathways; therapeutic development.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ALK and LTK receptors and species-specific respective ligands representative through evolution.
Figure 2
Figure 2
Receptor–ligand interactions. (a) LTK and Augα proposed mechanism of interaction by Savvides research group; (b) ALK and Augα proposed mechanism of interaction by Schlessinger, Klein, and Kalodimos research groups.
Figure 3
Figure 3
Organ-specific roles of ALK and Augα signaling axis.
See this image and copyright information in PMC

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