Cleavage and phosphorylation: important post-translational modifications of galectin-3

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Galectin-3, a unique chimeric β-galactoside-binding protein, is a multifunctional oncogenic protein implicated in diverse cellular processes.
• Post-translational modifications (PTMs) are crucial for modulating protein function, including activity, localization, and ligand interactions.
• Understanding galectin-3's PTMs is essential for elucidating its roles in normal cell biology and pathogenesis.

Purpose of the Study:

• To summarize and review reported post-translational modifications of galectin-3.
• To elucidate how cleavage and phosphorylation regulate galectin-3's function, multivalence, localization, and ligand interactions.

Main Methods:

• Literature review of studies reporting galectin-3 post-translational modifications.
• Analysis of findings related to galectin-3 cleavage by matrix metalloproteinases (MMPs), parasite proteases, and other proteases.
• Analysis of findings related to galectin-3 phosphorylation by kinases such as c-Abl, CKI, and GSK-3β.

Main Results:

• Cleavage of galectin-3 yields functional carbohydrate-recognition domains and N-terminal peptides, retaining lectin binding but losing multivalence.
• Phosphorylation (serine and tyrosine) of galectin-3 by specific kinases influences its cellular localization and associated signal transduction pathways.
• Both cleavage and phosphorylation are key regulatory mechanisms impacting galectin-3's biological activities.

Conclusions:

• Cleavage and phosphorylation are critical PTMs that diversify galectin-3's functions.
• These modifications alter galectin-3's multivalence, cellular localization, and ability to interact with ligands.
• Understanding these PTMs provides insights into galectin-3's roles in both normal physiology and disease pathogenesis.