Protein kinase Cα/β inhibitor Gö6976 promotes PC12 cell adhesion and spreading through membrane recruitment and activation of protein kinase Cδ

Jung, Sung Youn; Kim, O Bok; Kang, Hyun; Jang, Da Hyun; Min, Byung‐Moo; Yu, Frank H.

doi:10.1016/j.yexcr.2012.10.003

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…To this aim, the cells were treated for 24 hours with 3μM rottlerin, a PRKCD inhibitor (37), and were transfected with anti–miR-26a. As shown in Figure 5C, rottlerin pretreatment produced an increase in cyclin A and in phosphorylated p27 protein levels in mock-transfected cells (by ∼10% and by ∼80%, respectively).…”

Section: Resultsmentioning

confidence: 99%

miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

et al. 2013

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The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.

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Section: Resultsmentioning

confidence: 99%

miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

et al. 2013

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“…Gö6976 is an indolocarbazole compound widely used as a specific inhibitor of PKCα/β [6]. As a protein kinase C (PKC) inhibitor, it has shown remarkable effects in the treatment of collagen-induced arthritis [7], melanoma [8], nasopharyngeal carcinoma [9] and lung cancer [10].…”

Section: Introductionmentioning

confidence: 99%

The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo

et al. 2021

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Objectives: Chronic myeloid leukemia (CML) is a malignant tumor of the blood system. Gö6976, as a type of indolocarbazole and shows strong antitumor effects, but there have been no reports on the effect of Gö6976 on CML. The objectives of this research were: (1) to explore the impact of Gö6976 on CML in vitro and in vivo; and (2) to explore the drug toxicity of Gö6976 to normal cells and animals. Methods: K562 cells and CML mice were used to explore the effect of Gö6976 on CML. Peripheral blood mononuclear cells (PBMCs), CD34+ cells, and healthy mice were used to explore the drug toxicity of Gö6976. Results: Cell experiments showed that Gö6976 could inhibit the proliferation of K562 cells and enhance the inhibitory effects of imatinib at 5 μM and 10 μM, but it had little effect on CD34+ cells or PBMCs at concentrations less than 5 μM. Animal experiments showed that 2.5 mg/kg Gö6976 could effectively inhibit the development of CML in mice, and it had almost no effects on healthy mice at 2.5 mg/kg and 10 mg/kg. Discussion: Because of the direct inhibitory effect of Gö6976 on CML and its pharmacological enhancement effect on imatinib, it is foreseeable that Gö6976 could become a new type of anti-CML medicine. And the further research is needed. Conclusion: Our findings verified that Gö6976 could effectively inhibit CML in vitro and in vivo, and it is almost nontoxic to hematopoietic cells, immune cells, and healthy mice.

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“…On the contrary, the functional roles of other PKC isoforms in osteoclast adhesion and spreading have not been fully understood. PKC is known to activate downstream small GTPase cascades involved in the modulation of integrin-mediated cytoskeletal organization ( 17 , 18 ). For example, small GTPases (Rho and Rac) have been reported to organize and maintain cellular cytoskeletal structures in osteoclasts ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Selective regulation of osteoclast adhesion and spreading by PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling

2018

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Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin αvβ3 via “inside-out” and “outside-in” signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading. M-CSF- and OPN-induced osteoclast adhesion was achieved via activation of stepwise signals, including integrin αvβ3, PLCγ, PKCδ, and Rac1. Osteoclast spreading induced by M-CSF and OPN was shown to be controlled via sequential activation, consistent with the osteoclast adhesion processes. In contrast to osteoclast adhesion, osteoclast spreading induced by M-CSF and OPN was blocked via activation of PLCγ/PKCα/RhoA signaling. The combined results indicate that osteoclast adhesion and spreading are selectively regulated via PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling.

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Protein kinase Cα/β inhibitor Gö6976 promotes PC12 cell adhesion and spreading through membrane recruitment and activation of protein kinase Cδ

Cited by 7 publications

References 33 publications

miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo

Selective regulation of osteoclast adhesion and spreading by PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling

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