Protein Kinase D Specifically Mediates Apoptosis Signal-regulating Kinase 1-JNK Signaling Induced by H2O2 but Not Tumor Necrosis Factor

Zhang, Wei; Zheng, Shusen; Störz, Peter; Wang, Min

doi:10.1074/jbc.m414674200

Cited by 93 publications

(79 citation statements)

References 33 publications

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“…Multiple lines of evidence suggest PKD as a sensor of oxidative stress involved in several signaling pathways. [15][16][17] Therefore, we asked whether the interaction of PKD with DAPk might be regulated by oxidative stress. To induce oxidative stress, cells were treated with hydrogen peroxide (H 2 O 2 ) for 2min.…”

Section: Resultsmentioning

confidence: 99%

“…The finding that DAPk is necessary for the activation of JNK under oxidative stress, a process in which PKD has recently been shown to play an important role, 15 and that the association of DAPk and PKD is regulated by oxidative stress, raised the possibility that the DAPk-induced JNK activation may be mediated by PKD. Therefore, DAPk-induced JNK activation was assessed in DAPk overexpressing cells in which PKD activity was inhibited.…”

Section: Resultsmentioning

confidence: 99%

“…Phosphorylation of tyrosine 463 in PKD by Src, in concert with phosphorylation of the PKD activation loop by PKC-d, were shown to induce the activation of NF-kB by PKD leading to increased cellular survival. 16,17 More recently, Zhang et al, 15 demonstrated a PKC-independent activation mode of PKD under oxidative stress, which stimulates JNK phosphorylation via the activation of ASK1, consequently leading to cell death. However, how PKD is regulated in the latter cellular setting was not described.…”

Section: Discussionmentioning

confidence: 99%

“…Protein kinase D 1 (PKD 1, also known as PKC-m), 13,14 a kinase classified within the CAM kinase family, has been identified as one of the upstream regulators of this pathway, required for JNK activation and induction of cell death under oxidative stress conditions. 15 In general, two modes of PKD activation have been reported to function under oxidative stress, one depending on PKC activation 16,17 and the second, shown to be wired to the induction of JNK activity through ASK1, being PKC-independent. 15,18 Yet, the mechanism of the latter PKC-independent activation of PKD, initiating the induction of JNK signaling, remains undefined.…”

mentioning

confidence: 99%

“…15 In general, two modes of PKD activation have been reported to function under oxidative stress, one depending on PKC activation 16,17 and the second, shown to be wired to the induction of JNK activity through ASK1, being PKC-independent. 15,18 Yet, the mechanism of the latter PKC-independent activation of PKD, initiating the induction of JNK signaling, remains undefined. In this study, we examined a role for DAPk in response to oxidative stress.…”

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confidence: 99%

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DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Eisenberg‐Lerner

Kimchi

2007

Cell Death Differ

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The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Eisenberg‐Lerner

Kimchi

2007

Cell Death Differ

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Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress

Erol

2007

BioEssays

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Several protective cellular mechanisms protect against the accumulation of reactive oxygen species (ROS) and the concomitant oxidative stress. Therefore, any reduction in glucose or fatty acid flux into cells leading to a decrease in the production of reducing equivalents would also lead to a decreased ROS production and protect cells against oxidative stress. In the presence of insulin, FOXO proteins are localized from the nucleus to the cytoplasm and degraded. An increase in cellular glucose uptake will lead to increased production of ROS. This in turn activates the stress-responsive Jun-N-terminal kinase (JNK), which promotes nuclear translocation of FOXO proteins, upregulating some important target genes including stress resistance. Consequently, insulin resistance should result in decreased cellular ROS production. For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state.

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β‐catenin mediates alteration in cell proliferation, motility and invasion of prostate cancer cells by differential expression of E‐cadherin and protein kinase D1

Syed

Mak

et al. 2007

J of Cellular Biochemistry

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We have previously demonstrated that Protein Kinase D1 (PKD1) interacts with E-cadherin and is associated with altered cell aggregation and motility in prostate cancer (PC). Because both PKD1 and E-cadherin are known to be dysregulated in PC, in this study we investigated the functional consequences of combined dysregulation of PKD1 and E-cadherin using a panel of human PC cell lines. Gainand loss of function studies were carried out by either transfecting PC cells with fulllength E-cadherin and/or PKD1 cDNA or by protein silencing by siRNAs, respectively. We studied major malignant phenotypic characteristics including cell proliferation, motility, and invasion at the cellular level, which were corroborated with appropriate changes in representative molecular markers. Down regulation or ectopic expression of either E-cadherin or PKD1 significantly increased or decreased cell proliferation, motility, and invasion, respectively, and combined down regulation cumulatively influenced the effects. Loss of PKD1 or E-cadherin expression was associated with increased expression of the pro-survival molecular markers survivin, β-catenin, cyclin-D, and c-myc, whereas overexpression of PKD1 and/or E-cadherin resulted in an increase of caspases. The inhibitory effect of PKD1 and E-cadherin on cell proliferation was rescued by coexpression with β-catenin, suggesting that β-catenin mediates the effect of proliferation by PKD1 and E-cadherin. This study establishes the functional significance of combined dysregulation of PKD1 and E-cadherin in PC and that their effect on cell growth is mediated by β-catenin.

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Protein Kinase D Specifically Mediates Apoptosis Signal-regulating Kinase 1-JNK Signaling Induced by H2O2 but Not Tumor Necrosis Factor

Cited by 93 publications

References 33 publications

DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress

β‐catenin mediates alteration in cell proliferation, motility and invasion of prostate cancer cells by differential expression of E‐cadherin and protein kinase D1

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