Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes

Arun, Senthil Nathan; Kaddour‐Djebbar, Ismail; Shapiro, Brian A.; Bollag, Wendy B.

doi:10.1038/onc.2010.540

Cited by 22 publications

(27 citation statements)

References 41 publications

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“…In addition, PKD1 expression was shown to be up-regulated in mouse carcinomas and human hyperplastic disorders including basal cell carcinomas and psoriasis (4,12). More recently, PKD1 was implicated in radiationinduced apoptosis in mouse KCs (13). Our own genetic in vitro and in vivo studies in mouse skin did not support a role for PKD1 in epidermal homeostasis.…”

mentioning

confidence: 60%

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Ryvkin

Rashel

Gaddapara

et al. 2015

Journal of Biological Chemistry

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Background:The role of protein kinase D (PKD) signaling in human epidermis is unclear. Results: PKD isoforms have distinct and opposing growth regulatory functions in human keratinocytes. PKD3 is down-regulated upon differentiation and PKD3 silencing results in loss of keratinocyte proliferative potential. Conclusion: PKD signaling is essential for maintaining human epidermal homeostasis. Significance: PKD3 represents a potential drug target in hyperproliferative skin disorders.

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mentioning

confidence: 60%

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Ryvkin

Rashel

Gaddapara

et al. 2015

Journal of Biological Chemistry

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“…Although the PKD1-mediated NF-kB pathway has been shown to regulate cell survival in response to stimuli, such as H 2 O 2 and UVB, in a variety of studies (Arun et al, 2011;Song et al, 2009;Storz and Toker, 2003), the current study provides the first evidence that PKD2-and PKD3-mediated NF-kB pathway can promote activation of uPA signaling to regulate prostate cancer cell invasion. PKD2 and PKD3 both appeared to be important for general NF-kB activation and transactivation of uPA by NF-kB.…”

Section: Discussionmentioning

confidence: 86%

“…Three members of the PKD family have been identified to date, namely, PKD1 (PKCm), PKD2 and PKD3 (PKCn) (Wang, 2006). PKD has been implicated in various biological processes, such as cell proliferation (McEneaney et al, 2010;Papazyan et al, 2008;Wang, 2006), survival (Arun et al, 2011;Song et al, 2009), cell migration (Eiseler et al, 2010;Peterburs et al, 2009), differentiation (Jadali and Ghazizadeh, 2010;Kleger et al, 2011), inflammation (Kim et al, 2010b;Park et al, 2009) and vesicle transportation (Chen et al, 2009;Hausser et al, 2005;Lu et al, 2007). The role of PKDs in cancer invasion/metastasis has been increasingly recognized, and, of the three PKD isoforms, PKD1 has been the focus of most studies in this context.…”

Section: Introductionmentioning

confidence: 99%

PKD2 and PKD3 Promote Prostate Cancer Cell Invasion via uPA by Shifting Balance Between NF-κB and HDAC1

Zou

Zeng

et al. 2012

Journal of Cell Science

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SummaryAlthough protein kinase D3 (PKD3) has been shown to contribute to prostate cancer cell growth and survival, the role of PKD in prostate cancer cell motility remains unclear. Here, we show that PKD2 and PKD3 promote nuclear factor kappa B (NF-kB) signaling and urokinase-type plasminogen activator (uPA) expression/activation, which are crucial for prostate cancer cell invasion. Silencing of endogenous PKD2 and/or PKD3 markedly decreased prostate cancer cell migration and invasion, reduced uPA and uPA receptor (uPAR) expression and increased plasminogen activator inhibitor-2 (PAI-2) expression. These results were further substantiated by the finding that PKD2 and PKD3 promoted the activity of uPA and matrix metalloproteinase 9 (MMP9). Furthermore, depletion of PKD2 and/or PKD3 decreased the level of binding of the p65 subunit of NF-kB to the promoter of the gene encoding uPA (PLAU), suppressing transcriptional activation of uPA. Endogenous PKD2 and PKD3 interacted with inhibitor of NF-kB (IkB) kinase b (IKKb); PKD2 mainly regulated the phosphorylated IKK (pIKK)-phosphorylated IkB (pIkB)-IkB degradation cascade, p65 nuclear translocation, and phosphorylation of Ser276 on p65, whereas PKD3 was responsible for the phosphorylation of Ser536 on p65. Conversely, inhibition of uPA transactivation by PKD3 silencing was rescued by constitutive Ser536 p65 phosphorylation, and reduced tumor cell invasion resulting from PKD2 or PKD3 silencing was rescued by ectopic expression of p65. Interestingly, PKD3 interacted with histone deacetylase 1 (HDAC1), suppressing HDAC1 expression and decreasing its binding to the uPA promoter. Moreover, depletion of HDAC1 resulted in recovery of uPA transactivation in PKD3-knockdown cells. Taken together, these data suggest that PKD2 and PKD3 coordinate to promote prostate cancer cell invasion through p65 NF-kB-and HDAC1-mediated expression and activation of uPA.

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“…An increase in this phosphorylation in response to various PKD inducers could be detected using a phospho-specific antibody (38). A homologous tyrosine residue, Tyr-438, was found on PKD2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…4A), we further used an antibody developed against Tyr-463 within PKD1 for PKD2 analysis. This antibody was used efficiently for analyses of PKD1 phosphorylation in cells treated with various stimuli (38). Immunoblotting analysis of GST-PKD2 species expressed in 293T cells and purified by affinity beads revealed a robust IFN␣-inducible signal detected on wild-type PKD2 but not on Y438F mutant (Fig.…”

Section: Resultsmentioning

confidence: 99%

Tyrosine Phosphorylation of Protein Kinase D2 Mediates Ligand-inducible Elimination of the Type 1 Interferon Receptor

Zheng

Qian

Baker

et al. 2011

Journal of Biological Chemistry

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Type 1 interferons (including IFN␣/␤) activate their cell surface receptor to induce the intracellular signal transduction pathways that play an important role in host defenses against infectious agents and tumors. The extent of cellular responses to IFN␣ is limited by several important mechanisms including the ligand-stimulated and specific serine phosphorylation-dependent degradation of the IFNAR1 chain of Type 1 IFN receptor. Previous studies revealed that acceleration of IFNAR1 degradation upon IFN stimulation requires activities of tyrosine kinase TYK2 and serine/threonine protein kinase D2 (PKD2), whose recruitment to IFNAR1 is also induced by the ligand. Here we report that activation of PKD2 by IFN␣ (but not its recruitment to the receptor) depends on TYK2 catalytic activity. PKD2 undergoes IFN␣-inducible tyrosine phosphorylation on specific phospho-acceptor site (Tyr-438) within the plekstrin homology domain. Activated TYK2 is capable of facilitating this phosphorylation in vitro. Tyrosine phosphorylation of PKD2 is required for IFN␣-stimulated activation of this kinase as well as for efficient serine phosphorylation and degradation of IFNAR1 and ensuing restriction of the extent of cellular responses to IFN␣.Type 1 interferons (IFNs) play a critical role in modulating the immune responses against many pathogens and directly mounting the anti-viral defenses (for review, see Refs. 1-4). A family of these cytokines (including IFN␤ and diverse species of IFN␣) elicit the responses through the cognate Type 1 IFN receptor on the cell surface (5-7). Interaction of IFNAR1 2 and IFNAR2c chains of this receptor with the ligands triggers the signal transduction pathway that involves activation of the Janus kinases, JAK (TYK2 and JAK1) and subsequent tyrosine phosphorylation and ensuing activation of signal transducers and activators of transcription (STAT1 and STAT2). Transcriptionally active STAT1/2 further associate with IRF3, translocate to the nucleus and interact with IFN-stimulated response elements (ISRE) to induce de novo expression of the IFN-stimulated genes. Protein products of these mediate immunomodulatory and anti-viral responses as well as inhibit proliferation and survival of cells exposed to Type 1 IFN (for review, see Refs. 1-4).To alleviate these detrimental effects of Type 1 IFN, cells evolved to develop the mechanisms that limit the magnitude and duration of their responses to these cytokines. For example, some of the IFN-stimulated genes encode the proteins that may interfere with the recruitment of JAK to IFNAR chains (8). Additional modes of negative regulation that is commonly shared between most of cytokines-induced JAK-STAT pathways include inhibition of JAK activity/stimulation of JAK degradation by SOCS proteins, inhibition of tyrosine phosphorylation by phosphatases, and inhibition of STAT-induced transcription by PIAS (for review, see Refs. 6, 9). In addition to these modes of negative regulation, which occur in cells that have already executed the IFN-induced programs of signal tra...

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Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes

Cited by 22 publications

References 41 publications

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

PKD2 and PKD3 Promote Prostate Cancer Cell Invasion via uPA by Shifting Balance Between NF-κB and HDAC1

Tyrosine Phosphorylation of Protein Kinase D2 Mediates Ligand-inducible Elimination of the Type 1 Interferon Receptor

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