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Reconstruction of the ancestors of CMGC kinases reveals neofunctionalization via relaxed specificity intermediates (616.6)
Author(s) -
Holt Liam,
Howard Conor,
Kennedy Kristopher
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.616.6
Subject(s) - neofunctionalization , lineage (genetic) , kinase , evolutionary biology , biology , cyclin dependent kinase 1 , phylogenetics , genetics , gene , cell cycle
The mechanisms underlying the evolution of phosphoregulatory networks are poorly understood. We sought to understand the evolution of kinase specificity using the CMGC (Cdk1, MAPK, Gsk, CK) family as a model. This family has undergone dramatic functional diversification and therefore represents a useful model for kinase evolution. We have reconstructed the ancestral sequences for the entire CMGC kinase tree using a maximum likelihood method. We have synthesized, purified and profiled the specificities of the common ancestor of the CMGC family; and several ancestors leading to the Cdk1 paralog, Ime2. Our results indicate that the common ancestor of all CMGC kinases recognized the consensus sequence R‐P‐x‐S/T‐P. Additionally, we describe one neofunctionalization in detail: in the lineage leading to Ime2, ancestral kinases first broadened in specificity, and then lost their original +1 preference, ultimately shifting to the extant R‐P‐x‐S/T‐R preference in Ime2. This study reveals the ancestral events that led to diversification of kinase specificity in the CMGC family.