The yersinia virulence factor YopM forms a novel protein complex with two cellular kinases

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• Pathogenic Yersinia bacteria possess a virulence plasmid encoding effector proteins.
• These effectors, such as YopM, are crucial for Yersinia virulence by neutralizing host immune responses.
• The precise function of YopM within host cells remained largely unknown.

Purpose of the Study:

• To elucidate the cellular pathways targeted by the Yersinia effector YopM.
• To identify host proteins that interact with YopM in mammalian cells.

Main Methods:

• Proteins co-immunoprecipitating with YopM were isolated from mammalian cells.
• Protein identification was performed using mass spectrometry.
• Kinase activity and protein mobility were assessed in YopM-expressing and Yersinia-infected cells.

Main Results:

• YopM directly interacts with two host kinases: protein kinase C-like 2 (PRK2) and ribosomal S6 protein kinase 1 (RSK1).
• YopM expression stimulates the activity of both PRK2 and RSK1.
• RSK1 activation by YopM is direct, and its kinase activity is essential for YopM-mediated PRK2 activation.
• YopM influences RSK1 mobility in infected macrophages, independent of the MAPK pathway.

Conclusions:

• This study identifies PRK2 and RSK1 as the first characterized intracellular targets of YopM.
• YopM functions by stimulating the activity of PRK2 and RSK1, providing new insights into Yersinia virulence mechanisms.