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 language | English |
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Pages (from-to) | 376-392 |
Number of pages | 17 |
Journal | Molecular Biology and Evolution |
Volume | 36 |
Issue number | 2 |
DOIs | |
Publication status | Published - 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