A subcellular map of the human kinome

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The human kinome, consisting of 538 kinases, is crucial for cell signaling via protein phosphorylation.
• Understanding kinase subcellular localization is vital for elucidating normal cellular functions and disease pathogenesis.

Purpose of the Study:

• To create an image-based map of the human kinome, annotating the subcellular distribution of kinases.
• To investigate kinase localization patterns and identify novel cellular compartments occupied by kinases.

Main Methods:

• Expression of 456 epitope-tagged human kinases (85% of the kinome) in HeLa cells.
• Immunofluorescent microscopy was employed for imaging under standardized conditions.
• Annotation of kinase localizations across 10 distinct cellular compartments.

Main Results:

• The Kinome Atlas (KA) revealed kinase family-specific subcellular distributions.
• New kinase localizations were identified in mitochondria, plasma membrane, and extracellular space.
• The study demonstrated the involvement of liquid-liquid phase separation in kinase condensate formation and identified MOK as a mitochondrial kinase involved in respiration and stress response.

Conclusions:

• The Kinome Atlas provides a valuable subcellular map of the human kinome.
• This resource can refine our understanding of regulatory mechanisms in protein phosphorylation.
• The findings highlight novel kinase functions and locations, advancing cell signaling research.