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Investigating proximity‐mediated catalysis by a protein kinase: how docking affects MAPK specificity and processivity (802.16)
Author(s) -
Kaoud Tamer,
Dalby Kevin
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.802.16
Subject(s) - processivity , phosphorylation , kinase , dissociation (chemistry) , chemistry , mapk/erk pathway , docking (animal) , biophysics , protein kinase a , microbiology and biotechnology , biochemistry , enzyme , biology , polymerase , medicine , nursing
To understand how MAP kinases phosphorylate their substrates we previously investigated the mechanism of Ets‐1 phosphorylation by ERK2. Using pre‐steady state kinetic approaches we showed that the interaction between ERK2 and Ets‐1 is transient and that turnover is limited by both phosphorylation and ADP dissociation. Here, we investigate the mechanism of phosphorylation of ATF2 by JNK2 using pre‐steady state kinetics and mutagenesis. We find that JNK2 catalysis is limited by dissociation of ATF2 from JNK2 and that this difference in mechanism has significant implications for both the site‐specificity and processivity of the MAPK. We discuss these results in terms of a general mechanism for substrate turnover by protein kinases. Grant Funding Source : Supported by NIH GM59802 and Welch Foundation (F‐1390)