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ProPeL: A method to discover specific kinase motifs and predict target substrates
Author(s) -
Chou Michael F,
Prisic Sladjana,
Lubner Joshua M,
Church George M,
Husson Robert N,
Schwartz Daniel
Publication year - 2013
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.27.1_supplement.597.4
Subject(s) - kinase , computational biology , casein kinase 2 , biochemistry , proteome , map2k7 , casein kinase 1 , human proteome project , biology , sequence motif , protein kinase a , chemistry , proteomics , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , gene
Identification of kinase substrates is essential to understanding the role kinases play in normal and disease states. Kinases discriminate between potential substrates in part by recognizing linear sequence “motifs” of amino acids surrounding the phosphorylated residue. Current techniques for discovering kinase motifs are often expensive and labor intensive. The Pro teomic Pe ptide L ibrary (ProPeL) method is a novel approach to discover kinase specificity motifs de novo . Briefly, human kinases are expressed in E. coli and allowed to phosphorylate bacterial proteins. After enzymatic digestion of the bacterial lysate, tandem mass spectrometry is performed and motifs are extracted from the identified peptide sequences using the authors’ pLogo and motif‐x software. The ProPeL methodology successfully recapitulated the known and diverse motifs for human basophilic Protein Kinase A (PKA) and acidophilic Casein Kinase II (CK II). We then used the motifs determined using the ProPeL methodology to directly predict with high accuracy, potential target substrates of each kinase in the human proteome using the authors’ scan‐x program. We thus demonstrate the validity of the found motifs and the approach to search for potential substrates. This study was funded in part by grants from the University of Connecticut Research Foundation (DS) and Genomes to Life from US Department of Energy (GMC).