Plasma membrane requirements for 1α,25(OH)2D3 dependent PKC signaling in chondrocytes and osteoblasts

Boyan, Barbara D.; Wang, Liping; Wong, Kevin L.; Jo, Hanjoong; Schwartz, Zvi

doi:10.1016/j.steroids.2005.09.018

Cited by 50 publications

(40 citation statements)

References 25 publications

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“…Among many different PKC isoforms, PKCa is known to inhibit cell proliferation via p21 induction and suppress tumor formation in vivo (48,49). Several studies have previously shown that 1a,25(OH) 2 D 3 activates PKCa, and activation of this isoform acts as an antiproliferative signal (17,20,48,49). Our results also indicate that PKCa mediates the activation of Smad signaling, which is important for growth inhibition by the vitamin D 3 analogue Ro3582.…”

Section: Discussionmentioning

confidence: 99%

“…It was suggested that PKCa activation by 1a,25(OH) 2 D 3 was through the 1a,25(OH) 2 D 3 membrane-associated rapid response steroid binding protein (16,20). The classic VDR, which is known to translocate to the nucleus after ligand binding, has been proposed to be associated with caveolae in the plasma membrane and is responsible for the rapid response to vitamin D ligands (15,50).…”

Section: Discussionmentioning

confidence: 99%

“…Among many kinases, PKC has been shown to be regulated by 1a,25(OH) 2 D 3 and certain several vitamin D 3 analogues (17,19,20). The PKC family is a group of serine/threonine kinases known to regulate cell growth, apoptosis, differentiation, cell migration, and carcinogenesis in different types of cells and models (21,22).…”

Section: Introductionmentioning

confidence: 99%

“…The PKC family is a group of serine/threonine kinases known to regulate cell growth, apoptosis, differentiation, cell migration, and carcinogenesis in different types of cells and models (21,22). Boyan et al (19,20) suggest that a caveolar environment may play an important role in mediating the PKC activation by 1a,25(OH) 2 (17,18).…”

Section: Introductionmentioning

confidence: 99%

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Activation of Bone Morphogenetic Protein Signaling by a Gemini Vitamin D3 Analogue Is Mediated by Ras/Protein Kinase Cα

Lee

Paul

et al. 2007

Cancer Research

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Bone morphogenetic proteins (BMP) are members of the transforming growth factor-B superfamily, and they play an important role for embryonic development, for bone and cartilage formation, and during carcinogenesis. We have previously shown that the novel Gemini vitamin D 3 analogue, 1A,, inhibited cell proliferation and activated the BMP/Smad signaling pathway in MCF10AT1 breast epithelial cells. In this report, we investigated the upstream signaling pathways responsible for the activation of BMP/Smad signaling by Ro3582. Among seven different serine/threonine kinase inhibitors that we tested, protein kinase C (PKC) inhibitors blocked the effects of Ro3582 on the phosphorylation of Smad1/5, mRNA synthesis for BMP-2 and BMP-6, and cell growth in MCF10AT1 cells. Overexpression of PKCA, but not PKCE, PKCD or PKCZ isoforms, increased Ro3582-induced phosphorylation of Smad1/5, suggesting that PKCA mediates the activation of Smad signaling and inhibition of cell proliferation. Interestingly, the activation of Smad signaling by Ro3582 was shown in Ha-ras-transfected MCF10AT1 cells, but not in the parent cell line (MCF10A without Ras). Inhibiting Ras activity blocked the translocation of PKCA to the plasma membrane and the phosphorylation of Smad1/5 induced by Ro3582, indicating that Ras is necessary for the activation of PKCA and Smad signaling. In conclusion, Ro3582 inhibits cell proliferation and activates BMP/Smad signaling via a Ras and PKCA pathway in breast epithelial cells. [Cancer Res 2007;67(24):11840-7]

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Activation of Bone Morphogenetic Protein Signaling by a Gemini Vitamin D3 Analogue Is Mediated by Ras/Protein Kinase Cα

Lee

Paul

et al. 2007

Cancer Research

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“…Moreover, a recent study has suggested that polymorphisms in human VDR may also facilitate breast cancer progression [8]. Upon Vit D binding to target VDRs it can regulate various cellular and physiologic functions using both rapid non-genomic and genomic mechanisms [9][10][11][12]. Vit D…”

Section: Introductionmentioning

confidence: 99%

Estrogen Activation of CaM Kinases and Transcription Is Blocked by Vitamin D in MCF-7 Breast Cancer Cells

John¹,

Do²,

Amanda³

et al. 2017

JAMB

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Abstract. Calcium/calmodulin-dependent protein kinase (CaM Kinase) proteins are targets of hormones and growth factors and regulate cancer cell growth, apoptosis and migration. The hormone estrogen (E2) utilizes CaM Kinases to activate the Extracellular-signal regulated kinase (ERK) leading to MCF-7 breast cancer cell growth. The hormone Vitamin D (Vit D) may inhibit breast cancer cell growth however the cellular mechanisms of Vit D action remain to be elucidated. Within the present study we provide data that E2 stimulation of MCF-7 cells activates CaM Kinase Kinase (CaM KK), CaM KI, and ERK and the transcription factors Elk-1 and SRF. E2 treatment of MCF-7 cells potently stimulated Elk-1/SRF directed transcription of SRE-luciferase reporters. E2 activation of ERK, Elk-1, SRF and SRE-dependent luciferase activities were blocked by treating cells with the CaM KK inhibitor, STO-609, and the ERK inhibitor, U0126. Moreover, siRNAs directed against CaM KK and ERK blocked transcription factor phosphorylation and luciferase activity. Treatment of cells with Vit D, the hormone Epinephrine (Epi), or Forskolin, prevented E2 activation of CaM KK and ERK. Interestingly, Vit D promoted a PKA-dependent phosphorylation and inhibition of CaM KK as well as its association with 14-3-3. Epi and Vit D treatment of cells blocked the ability of E2 to active Elk-1 and SRE-luciferase activity. This data suggests an important role for CaM KK and ERK in regulating transcription downstream of E2 in MCF-7 cells. Our results also suggest that Vit D treatment of MCF-7 cells utilizes a unique PKA-dependent mechanism to block E2 activation of CaM KK, ERK and transcription.

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Expression profiling of vitamin D treated primary human keratinocytes

Moll

Sander

Frischauf

et al. 2006

J of Cellular Biochemistry

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Vitamin D has attracted much attention by its ability to stop cell proliferation and induce differentiation, which became of particular interest for the treatment of cancer and psoriasis. We performed an expression profile of 12 hours and 24 hours 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) treated primary human keratinocytes, to determine the changes in gene expression induced by the steroid in order to improve our understanding of the biological activity of 1alpha,25(OH)(2)D(3). This we expect to be useful for establishing a test system for vitamin D analogs or might open new therapeutic targets or uses for the hormone. For the filter array experiments a non-redundant set of 2135 sequence verified EST clones was used. The normalized raw data of 2 filters per time point were combined and subjected to SAM analysis to further increase the statistical significance. 86 positive and 50 negative genes were identified after 12 h. The numbers went down to 43 positive and 1 negative gene after 24 h of treatment. Fifteen genes are up-regulated over a longer period of time (12 h and 24 h). Results were verified by real-time PCR and/or Northern blots. Targets identified are involved in intracellular signaling, transcription, cell cycle, metabolism, cellular growth, constitution of the extracellular matrix or the cytoskeleton and apoptosis, immune responses, and DNA repair, respectively. Expression profiles showed an initial stop of proliferation and induction of differentiation, and resumed proliferation after prolonged incubation, most likely due to degradation of the hormone.

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Plasma membrane requirements for 1α,25(OH)2D3 dependent PKC signaling in chondrocytes and osteoblasts

Cited by 50 publications

References 25 publications

Activation of Bone Morphogenetic Protein Signaling by a Gemini Vitamin D3 Analogue Is Mediated by Ras/Protein Kinase Cα

Activation of Bone Morphogenetic Protein Signaling by a Gemini Vitamin D3 Analogue Is Mediated by Ras/Protein Kinase Cα

Estrogen Activation of CaM Kinases and Transcription Is Blocked by Vitamin D in MCF-7 Breast Cancer Cells

Expression profiling of vitamin D treated primary human keratinocytes

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