Evolution of protein kinase substrate recognition at the active site

Area of Science:

• Biochemistry
• Evolutionary Biology
• Molecular Biology

Background:

• Protein kinases regulate cellular processes via phosphorylation.
• Kinase specificity is partly determined by kinase-substrate motifs.
• The evolutionary origin of new kinase target motifs is largely unknown.

Purpose of the Study:

• To investigate the evolutionary timing of protein kinase target motif acquisition.
• To understand how kinase specificity has evolved over time.
• To determine the distribution of kinase motifs across eukaryotes and prokaryotes.

Main Methods:

• Analysis of sequence variation in early kinase evolution.
• Examination of kinase specificity models based on known target sites.
• Phylogenetic analysis of phosphorylation data across 48 eukaryotic species.

Main Results:

• Early kinase evolution featured significant changes in specificity-determining residues.
• Specificity remained largely conserved in recent kinase duplications.
• Most eukaryotic phosphorylation motifs are broadly distributed in eukaryotes but absent in prokaryotes.

Conclusions:

• Eukaryotic kinase motifs were predominantly acquired around the time of the last eukaryotic common ancestor.
• Early expansions of the protein kinase fold rapidly explored diverse target motifs.
• This suggests a conserved set of kinase-substrate interactions established early in eukaryotic evolution.