Figure 1
Phylogenetic analysis reveals the absence of phosphomimetic substitutions in the activation loop (AL) of AGC kinases. (A) Comparison of AL and hydrophobic motif (HM) sequences across the 61 human AGC kinases. Phosphorylatable residues in AL and HM are represented in green. Phosphomimetic substitutions are represented in blue. Substitutions with neither phosphorylatable nor phosphomimetic amino acids are represented in gray. The scale bar represents the number of amino acid substitutions per site. (B) Representation of the proportion of amino acid substitutions of the phosphorylatable residues across human AGC kinases. (C) Phylogenetic relationship of Naegleria gruberi p70S6K, showing a phosphomimetic substitution in the HM sequence, with p70S6K homologues in other eukaryotic organisms. (D) Phylogenetic relationship among some of the Arabidopsis thaliana AGC kinases showing phosphomimetic substitution in HM of kinases belonging to AGC1 class. (E) Meta-analysis of the effects of artificial phosphomimetic substitutions in different AGC kinases. The results of phosphomimetic substitution on the kinase activity were classified into two groups, one showing a consistent reduction of the kinase activity (residual kinase activity less than 50% of wild type protein), the other showing at least 50% of kinase activity of the wild type protein.
