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Updated: Jun 27, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

Co-Phosphoregulatory Network Underlying Functional Coherence of TLK1 and TLK2 Kinase Paralogs

Jishna Vijayan1, Suhail Subair1, Mukhtar Ahmed2

  • 1Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India.

International Journal of Molecular Sciences
|June 26, 2026
PubMed

Insights

Tousled-like kinases 1 and 2 (TLK1 and TLK2) are key regulators of DNA replication and chromatin organization. This study reveals their distinct phosphoregulatory networks, highlighting paralog-specific roles in genome stability and cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Tousled-like kinases 1 and 2 (TLK1 and TLK2) are paralogous serine/threonine kinases with similar sequences but distinct functions.
  • These kinases are involved in critical cellular processes including DNA replication, DNA damage response, and chromatin organization.

Purpose of the Study:

  • To elucidate the paralog-specific co-phosphoregulatory networks of TLK1 and TLK2.
  • To understand how these networks contribute to the functional divergence of TLK1 and TLK2 in cellular processes and disease.

Main Methods:

  • Comprehensive analysis of 3825 human phosphoproteomic datasets.
  • Identification of predominant phosphosites for TLK1 and TLK2.
  • Co-phosphoregulation network analysis to identify interacting proteins and upstream kinases.

Main Results:

  • Identified key phosphosites: S134 and T38 for TLK1; S73, S99, and S111 for TLK2.
  • TLK1 networks are linked to DNA damage signaling (e.g., ABRAXAS1, PML, RAD9A).
  • TLK2 networks are associated with chromatin remodeling and replication (e.g., CHD4, DOT1L, NASP, RNF20) and cell-cycle progression via CDKs.

Conclusions:

  • TLK1 and TLK2 exhibit paralog-specific co-phosphoregulatory networks, driving functional divergence.
  • TLK1 may play a role in checkpoint activation, while TLK2 is involved in replication-coupled chromatin maintenance.
  • These findings offer insights into the roles of TLK1/TLK2 in cancer, therapeutic resistance, and neurodevelopmental disorders.
Keywords:
TLK1TLK2Tousled-like kinasesco-phosphoregulationphosphoproteomics

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