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Identification of New JNK Substrate Using ATP Pocket Mutant JNK and a Corresponding ATP Analogue
Journal article   Open access   Peer reviewed

Identification of New JNK Substrate Using ATP Pocket Mutant JNK and a Corresponding ATP Analogue

Hasem Habelhah, Kavita Shah, Lan Huang, Alma L Burlingame, Kevan M Shokat and Ze'ev Ronai
The Journal of biological chemistry, Vol.276(21), pp.18090-18095
05/25/2001
DOI: 10.1074/jbc.M011396200
PMID: 11259409
url
https://doi.org/10.1074/jbc.M011396200View
Published (Version of record) Open Access

Abstract

Modification of the ATP pocket on protein kinases allows selective use of an ATP analogue that exhibits high affinity for the altered kinases. Using this approach, we altered the ATP-binding site on JNK and identifiedN 6-(2-phenythyl)-ATP, a modified form of ATP that exhibits high specificity and affinity for the modified, but not the wild type form, of JNK. Using modified JNK and its ATP analogue enables the detection of novel JNK substrates. Among substrates identified using this approach is heterogeneous nuclear ribonucleoprotein K, which is involved in transcription and post-transcriptional mRNA metabolism. The newly identified substrate can be phosphorylated by JNK on amino acids 216 and 353, which contribute to heterogeneous nuclear ribonucleoprotein K mediated transcriptional activities.

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