TBCK (TBC1 Domain Containing Kinase) has been at the forefront of research due to its role in various biological processes and diseases, including neurodevelopmental disorders and cancers. Despite its name, TBCK's precise function and classification as a true kinase or pseudokinase remain subjects of investigation.
This recent study explores TBCK’s kinase domain, revealing that it lacks several critical motifs necessary for conventional kinase activity. Notably, mutations in TBCK have been linked to TBCK-related encephalopathy, a rare neurogenetic condition, and various cancers. The absence of the essential “D” residue in the catalytic and activation loops positions TBCK as a pseudokinase. However, findings suggest that TBCK might influence protein phosphorylation indirectly or retain minimal basal kinase activity.
Key Insights:
- Neurogenetic Disorders: Mutations in TBCK's TBC domain are associated with disrupted mTOR signaling, contributing to conditions like hypotonia, epilepsy, and intellectual disabilities.
- Cancer Research: TBCK's involvement in tumor growth suppression and its impact on signaling pathways like STAT3 are promising areas for targeted therapies.
- Molecular Structure: Advanced tools, including AlphaFold2 and RNA-seq data, have provided deeper insights into TBCK’s domain structure and potential interactions.
The study underscores the importance of high-throughput analyses to identify TBCK’s interacting partners, paving the way for breakthroughs in treating neurogenetic disorders and cancer.
Full Text: https://www.igminresearch.com/articles/html/igmin238
PDF Link: https://www.igminresearch.com/articles/pdf/igmin238.pdf
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