Docking Interactions in the c-Jun N-terminal Kinase Pathway Export

@article{citeulike:2698308, abstract = {The c-Jun N-terminal kinase (JNK) signaling pathway is a major mediator of stress responses in cells. Similar to other mitogen-activated protein kinases (MAPKs), JNK activity is controlled by a cascade of protein kinases and by protein phosphatases, including dual-specificity MAPK phosphatases. Components of the JNK pathway associate with scaffold proteins that modulate their activities and cellular localization. The JNK-interacting protein-1 (JIP-1) scaffold protein specifically binds JNK, MAPK kinase 7 (MKK7), and members of the mixed lineage kinase (MLK) family, and regulates JNK activation in neurons. In this study we demonstrate that distinct regions within the N termini of MKK7 and the MLK family member dual leucine zipper kinase (DLK) mediate their binding to JIP-1. We have also identified amino acids in JNK required for: (a) binding to JIP-1 and for JIP-1-mediated JNK activation, (b) docking to MAPK kinase 4 (MKK4) and efficient phosphorylation by MKK4, and (c) docking to its substrate c-Jun and efficient c-Jun phosphorylation. None of the amino acids identified were essential for JNK docking to MKK7 or the dual-specificity phosphatase MAPK phosphatase 7 (MKP7). These findings uncover molecular determinants of JIP-1 scaffold complex assembly and demonstrate that there are overlapping, but also distinct, binding determinants within JNK that mediate interactions with scaffold proteins, activators, phosphatases, and substrates. 10.1074/jbc.M311841200}, author = {Mooney, Lorraine M. and Whitmarsh, Alan J.}, citeulike-article-id = {2698308}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M311841200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/279/12/11843}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/14699111}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=14699111}, day = {19}, doi = {10.1074/jbc.M311841200}, journal = {J. Biol. Chem.}, keywords = {bzip\_signal\_transduction}, month = {March}, number = {12}, pages = {11843--11852}, posted-at = {2008-04-21 23:08:02}, priority = {2}, title = {Docking Interactions in the c-Jun N-terminal Kinase Pathway}, url = {http://dx.doi.org/10.1074/jbc.M311841200}, volume = {279}, year = {2004} }

TY - JOUR ID - citeulike:2698308 L3 - citeulike-article-id:2698308 N2 - The c-Jun N-terminal kinase (JNK) signaling pathway is a major mediator of stress responses in cells. Similar to other mitogen-activated protein kinases (MAPKs), JNK activity is controlled by a cascade of protein kinases and by protein phosphatases, including dual-specificity MAPK phosphatases. Components of the JNK pathway associate with scaffold proteins that modulate their activities and cellular localization. The JNK-interacting protein-1 (JIP-1) scaffold protein specifically binds JNK, MAPK kinase 7 (MKK7), and members of the mixed lineage kinase (MLK) family, and regulates JNK activation in neurons. In this study we demonstrate that distinct regions within the N termini of MKK7 and the MLK family member dual leucine zipper kinase (DLK) mediate their binding to JIP-1. We have also identified amino acids in JNK required for: (a) binding to JIP-1 and for JIP-1-mediated JNK activation, (b) docking to MAPK kinase 4 (MKK4) and efficient phosphorylation by MKK4, and (c) docking to its substrate c-Jun and efficient c-Jun phosphorylation. None of the amino acids identified were essential for JNK docking to MKK7 or the dual-specificity phosphatase MAPK phosphatase 7 (MKP7). These findings uncover molecular determinants of JIP-1 scaffold complex assembly and demonstrate that there are overlapping, but also distinct, binding determinants within JNK that mediate interactions with scaffold proteins, activators, phosphatases, and substrates. 10.1074/jbc.M311841200 IS - 12 JF - J. Biol. Chem. EP - 11852 TI - Docking Interactions in the c-Jun N-terminal Kinase Pathway VL - 279 SP - 11843 KW - bzip_signal_transduction AU - Mooney, Lorraine AU - Whitmarsh, Alan PY - 2004/03/19/ UR - http://dx.doi.org/10.1074/jbc.M311841200 ER -