Differential targeting of the stress mitogen-activated protein kinases to the c-Jun dimerization protein 2.
The mitogen-activated kinases are structurally related proline-directed serine/threonine kinases that phosphorylate similar phosphoacceptor sites and yet, in vivo, they exhibit stringent substrate specificity. Specific targeting domains (kinase docking domains) facilitate kinase-substrate interaction and play a major role in substrate specificity determination. The c-Jun N-terminal kinase (JNK) consensus docking domain comprises of a KXXK/RXXXXLXL motif located in the delta-domain of the c-Jun N-terminal to the phosphoacceptor site. The c-Jun dimerization protein 2 is phosphorylated by JNK on Thr-148. Activating transcription factor 3 (ATF3) is a basic leucine zipper protein which is highly homologous to c-Jun dimerization protein 2 (JDP2), especially within the threonine/proline phosphoacceptor site, Thr-148. Nevertheless, ATF3 does not serve as a JNK substrate in vitro or in vivo. Using ATF3 and JDP2 protein chimaeras, we mapped the JNK-docking domain within JDP2. Although a JNK consensus putative docking site is located within the JDP2 leucine zipper motif, this domain does not function to recruit JNK to JDP2. A novel putative docking domain located C-terminally to the JDP2 phosphoacceptor site was identified. This domain, when fused to the ATF3 heterologous phosphoacceptor site, can direct its phosphorylation by JNK. In addition, although the novel JNK-docking domain was found to be necessary for p38 phosphorylation of JDP2 on Thr-148, it was not sufficient to confer JDP2 phosphorylation by the p38 kinase.
Katz
Sigal
S
Department of Molecular Genetics, The B. Rappaport Faculty of Medicine, 7 Efron St. Bat Galim, The Technion-Israel Institute of Technology, Haifa 31096, Israel.
Aronheim
Ami
A
D016475:3T3 Cells; D051700:Activating Transcription Factor 3; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D005982:Glutathione Transferase / Q000378:metabolism; D007930:Leucine / Q000737:chemistry; D020935:MAP Kinase Signaling System; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D051700:Activating Transcription Factor 3; C491386:Jundp2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D005982:Glutathione Transferase; D007930:Leucine