The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The regulation, function, and intracellular distribution of human Lats2 (Large tumor suppressor kinase 2), a member of the Lats kinase family, remain largely uncharacterized.
• Lats1, a related kinase, is known to be phosphorylated during mitosis and localizes to the mitotic apparatus.

Purpose of the Study:

• To investigate the regulation of human Lats2, specifically focusing on its potential phosphorylation by Aurora-A kinase.
• To determine the functional consequences of Lats2 phosphorylation, particularly its role in intracellular localization.

Main Methods:

• In vitro kinase assays to identify phosphorylation sites on Lats2.
• Development and utilization of a phospho-specific antibody to detect Lats2 phosphorylation at S83 in vivo.
• Co-immunoprecipitation and immunofluorescence microscopy to assess Lats2-Aurora-A interactions and co-localization at centrosomes.
• Experimental inhibition of Aurora-A activity to evaluate the impact on Lats2 phosphorylation and localization.

Main Results:

• Human Lats2 is identified as a novel phosphorylation target of Aurora-A kinase.
• Phosphorylation of Lats2 by Aurora-A occurs specifically at serine residue 83 (S83), both in vitro and in vivo.
• Lats2 and Aurora-A exhibit transient interactions and co-localize at centrosomes throughout the cell cycle.
• Inhibition of Aurora-A kinase activity partially disrupts the centrosomal localization of Lats2.

Conclusions:

• Serine 83 (S83) of human Lats2 is a direct phosphorylation target of Aurora-A kinase.
• Aurora-A-mediated phosphorylation of Lats2 at S83 plays a significant role in regulating its centrosomal localization.