Interacting JNK-docking Sites in MKK7 Promote Binding and Activation of JNK Mitogen-activated Protein Kinases

Ho, David T.; Bardwell, A. Jane; Grewal, Seema; Iverson, Corey; Bardwell, Lee

doi:10.1074/jbc.m601010200

Cited by 69 publications

(79 citation statements)

References 62 publications

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“…Thus, the role of JIP1 in the JNK pathway may be mechanistically very different from prototypical signaling scaffolds, such as the Saccharomyces cerevisiae Ste5 protein that increases overall signaling spec-ificity by binding different pathway components simultaneously and so stimulates pathway throughput via allosteric regulatory mechanisms (123). In addition, the mammalian MKK7 shows high specificity for the JNKs (124)(125)(126), and so the mammalian MKK7-JNK pathway would not need to rely on additional scaffold proteins to provide pathway specificity. However, in this context it should be appreciated that scaffold proteins may admit a number of negative and/or positive feedback circuits to set the appropriate level of JNK activity for different subcellular compartments and physiological states.…”

Section: Scaffold Proteins In Jnk Signalingmentioning

confidence: 99%

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

409

350

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SUMMARYThe c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.

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Section: Scaffold Proteins In Jnk Signalingmentioning

confidence: 99%

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

409

350

View full text Add to dashboard Cite

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“…Emerging studies in the last few years have provided compelling evidence that these binding sites for docking motifs play a key role in determining the substrate specificity of MAPKs (Biondi and Nebreda, 2003;Tanoue and Nishida, 2003;Dimitri et al, 2005;Ho et al, 2006). The best described docking motif is known as docking site for ERK and JNK (DEJL) or D motif (Chang et al, 2002;Lee et al, 2004;Callaway et al, 2005;Zhou et al, 2006) which posses the general pattern (Arg/Lys) 1À2 -(X) 2-6 -+ A -X-+ B , where + A and + B are hydrophobic residuesleucine (Leu), isoleucine (Ile) or valine (Val).…”

Section: The Structure Of Mapksmentioning

confidence: 99%

MAP kinases and the control of nuclear events

2007

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The mitogen-activated protein kinases (MAPKs) are a family of serine/threonine kinases that play an essential role in signal transduction by modulating gene transcription in the nucleus in response to changes in the cellular environment. They include the extracellular signal-regulated protein kinases (ERK1 and ERK2); c-Jun N-terminal kinases (JNK1, JNK2, JNK3); p38s (p38a, p38b, p38c, p38d) and ERK5. The molecular events in which MAPKs function can be separated in discrete and yet interrelated steps: activation of the MAPK by their upstream kinases, changes in the subcellular localization of MAPKs, and recognition, binding and phosphorylation of MAPK downstream targets. The resulting pattern of gene expression will ultimately depend on the integration of the combinatorial signals provided by the temporal activation of each group of MAPKs. This review will focus on how the specificity of signal transmission by MAPKs is achieved by scaffolding molecules and by the presence of structural motifs in MAPKs that are dynamically regulated by phosphorylation and protein-protein interactions. We discuss also how MAPKs recognize and phosphorylate their target nuclear proteins, including transcription factors, co-activators and repressors and chromatin-remodeling molecules, thereby affecting an intricate balance of nuclear regulatory molecules that ultimately control gene expression in response to environmental cues.

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“…Analysis of Sab indicated it had a kinase-interacting motif (KIM domain) similar to that of many other known JNK-interacting proteins (15)(16)(17)(18). The JNK-interacting protein-1 is most well studied, and a cell-permeable version of this peptide has been shown to be efficacious in numerous efficacy models ranging from PD (13) to cerebral ischemia (19) and diabetes (20).…”

mentioning

confidence: 99%

Blocking c-Jun N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-Hydroxydopamine-induced Toxicity in Vitro and in Vivo

Chambers

Howard

LoGrasso

2013

Journal of Biological Chemistry

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Background:Little is known about the role for JNK mitochondrial signaling in neuronal cell death. Results: Global and mitochondrial inhibition of JNK protects against 6-OHDA-induced neuronal loss in the SNpc. Conclusion: Blocking JNK mitochondrial translocation or JNK inhibition may be an effective treatment for neuronal death in Parkinson disease. Significance: These findings suggest a new molecular target for JNK inhibition.

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Interacting JNK-docking Sites in MKK7 Promote Binding and Activation of JNK Mitogen-activated Protein Kinases

Cited by 69 publications

References 62 publications

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

MAP kinases and the control of nuclear events

Blocking c-Jun N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-Hydroxydopamine-induced Toxicity in Vitro and in Vivo

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