Irreversible Activation of Rho-activated Kinases Resulted from Evolution of Proteolytic Sites within Disordered Regions in Coiled-coil Domain

Paolo Armando Gagliardi, Luca Primo

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of Rho-associated protein kinase 1 (ROCK1) and myotonic dystrophy kinase-related CDC42-binding kinase alpha (MRCKα) by caspases during apoptosis in vertebrates represents a prototypical example of co-option of kinases by proteases. How caspases acquired the ability to control these proteins during evolution of vertebrates is still unknown. Here, we report a phylogenetic and molecular study on the acquisition of caspase-cleavage sites in the family of Rho-activated kinases (RaKs). We demonstrate that the acquisition of such sites has more frequently occurred in identifiable intrinsically disordered regions (IDRs) within or flanking the coiled-coil domain. Thanks to computational identification of IDRs in protein sequences of different organisms, we predicted and validated the independent evolution of two caspase-cleavage sites in ROCK of arthropods and the loss of one of the MRCKα caspase-cleavage sites in ray-finned fishes. In conclusion, we shed light on the propensity of RaKs to evolve novel proteolytic sites, causing kinase activation and uniform subcellular distribution.

Original languageEnglish
Pages (from-to)376-392
Number of pages17
JournalMolecular Biology and Evolution
Volume36
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

Keywords

  • Amino Acid Sequence
  • Animals
  • Arthropods/genetics
  • Catalytic Domain
  • Chordata/genetics
  • Evolution, Molecular
  • Phylogeny
  • Protein Domains/genetics
  • Proteolysis
  • rho-Associated Kinases/genetics

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