Citron kinase interacts with LATS2 and inhibits its activity by occluding its hydrophobic phosphorylation motif

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The Hippo pathway, involving large tumor suppressor kinase (LATS1/2) and yes-associated protein (YAP), is vital for tissue homeostasis.
• Citron kinase (CIT) has known roles in cytokinesis, but its connection to the Hippo pathway was unexplored.

Purpose of the Study:

• To investigate the molecular crosstalk between citron kinase (CIT) and the Hippo pathway.
• To elucidate the role of CIT in regulating LATS2 and YAP activity.

Main Methods:

• Proteomic analysis to identify potential binding partners.
• Co-immunoprecipitation and Western blotting to confirm protein interactions and phosphorylation states.
• Genetic interaction studies in Drosophila melanogaster.

Main Results:

• Citron kinase (CIT) functions as a scaffold protein, bridging LATS2 and YAP.
• CIT directly inhibits LATS2 phosphorylation at the hydrophobic motif by MST1, leading to LATS2 inactivation.
• Activated YAP signaling was observed due to CIT's intervention.
• The Drosophila homolog of CIT, Sticky, interacts with Warts to regulate eye development.

Conclusions:

• Citron kinase (CIT) is a novel regulator of the Hippo pathway.
• CIT's interaction with LATS2 modulates Hippo pathway signaling, impacting YAP activity.
• The findings highlight a new mechanism controlling tissue homeostasis and development.