VASCULAR ENDOTHELIAL GROWTH FACTOR INDUCES PROTEIN KINASE C (PKC)‐DEPENDENT Akt/PKB ACTIVATION AND PHOSPHATIDYLINOSITOL 3′‐KINASE‐MEDIATED PKCδ PHOSPHORYLATION: ROLE OF PKC IN ANGIOGENESIS

Gliki, Georgia; Wheeler‐Jones, Caroline P.D.; Zachary, Ian

doi:10.1006/cbir.2002.0926

Cited by 18 publications

(3 citation statements)

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“…[12] Bisindolylmaleimide I reduced HUVEC vasculogenesis by about half at concentrations above 1 μm, also consistent with earlier reports. [60,61] For HRMVECs, the compound showed no clear inhibition of the endothelial network as previously reported. [12] Plerixafor had a similar effect on both cell types.…”

Section: High-throughput 3d Vasculogenesis Models Enable Direct Compa...supporting

confidence: 72%

Precision Culture Scaling to Establish High‐Throughput Vasculogenesis Models

Dennison,

Fusenig,

Grönnert

et al. 2024

Adv Healthcare Materials

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Hydrogel‐based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high‐throughput screening workflows remains challenging. In this study, a new Precision Culture Scaling (PCS‐X) methodology combines statistical techniques (Design of Experiment and Multiple Linear Regression) with automated, parallelized experiments and analyses to customize hydrogel‐based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells. Variations of cell density, growth factor supplementation and media composition are systematically explored to induce vasculogenesis in endothelial mono‐ and cocultures with mesenchymal stromal cells or retinal microvascular pericytes in 384‐well plate formats. The developed cultures are shown to respond to vasculogenesis inhibitors in a compound‐ and dose‐dependent manner, demonstrating the scope and power of PCS‐X in creating parallelized tissue and disease models for drug discovery and individualized therapies.This article is protected by copyright. All rights reserved

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Section: High-throughput 3d Vasculogenesis Models Enable Direct Compa...supporting

confidence: 72%

Precision Culture Scaling to Establish High‐Throughput Vasculogenesis Models

Dennison,

Fusenig,

Grönnert

et al. 2024

Adv Healthcare Materials

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“…In the case of PKCa, this residue is Thr 497 [Bornancin and Parker, 1996], while for PKCe, it is Thr 566 [Le Good et al, 1998]. PDK-1 also phosphorylates Thr 505 of PKCd, and Thr 410 of PKCz [Chou et al, 1998;Gliki et al, 2002]. This first phosphorylation step triggers autophosphorylation at two other sites in the catalytic domain, the first in the ''turn motif,'' and the last in the ''hydrophobic motif '' [Dutil et al, 1998].…”

mentioning

confidence: 99%

Role of protein kinase C in arginine vasopressin‐stimulated ERK and p70S6 kinase phosphorylation

Ghosh

Bedolla

Thomas

et al. 2004

J of Cellular Biochemistry

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We previously showed in rat renal glomerular mesangial cells, that arginine vasopressin (AVP)-stimulated cell proliferation was mediated by epidermal growth factor receptor (EGF-R) transactivation, and activation (phosphorylation) of ERK1/2 and p70S6 kinase (Ghosh et al. [2001]: Am J Physiol Renal Physiol 280:F972-F979]. In this paper, we extend these observations and show that different protein kinase C (PKC) isoforms play different roles in mediating AVP-stimulated ERK1/2 and p70S6 kinase phosphorylation and cell proliferation. AVP treatment for 0-60 min stimulated the serine/threonine phosphorylation of PKC isoforms alpha, delta, epsilon, and zeta. The activation of PKC was dependent on EGF-R and phosphatidylinositol 3-kinase (PI3K) activation. In addition, inhibition of conventional and novel PKC isoforms by chronic (24 h) exposure to phorbol 12-myristate 13-acetate (PMA) inhibited AVP-induced activation of ERK and p70S6 kinase as well as EGF-R phosphorylation. Rottlerin, a specific inhibitor of PKCdelta, inhibited both ERK and p70S6 kinase phosphorylation and cell proliferation. In contrast, a PKCepsilon translocation inhibitor decreased ERK1/2 activation without affecting p70S6 kinase or cell proliferation, while a dominant negative PKCzeta (K281W) cDNA delayed p70S6 kinase activation without affecting ERK1/2. On the other hand, Gö6976, an inhibitor of conventional PKC isoforms, did not affect p70S6 kinase, but stimulated ERK1/2 phosphorylation without affecting cell proliferation. Our results indicate that PKCdelta plays an important role in AVP-stimulated ERK and p70S6 kinase activation and cell proliferation.

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“…In this sense, signaling through phosphatidylinositol-3-kinase (PI3K) and its downstream kinase Akt has been widely implicated in cell survival [29], therefore the relationship between PKC activation and Akt function has been subject of intense investigation. Some studies have shown that PKCs activate Akt in endothelial and myeloid cells, an effect that has been attributed in most cases to the classical PKC isoforms [30,31]. Nevertheless, it was also shown that in normal mammary cells PKC overexpression conferred resistance against cytotoxic drugs throughout a substantial elevation in the levels of activated Akt [25].…”

Section: Pkc Downstream Signaling Pathwaysmentioning

confidence: 99%

The Pros and Cons of Targeting Protein Kinase c (PKC) in the Management of Cancer Patients

Leskow¹,

Krasnapolski²,

Urtreger

2011

CPB

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In the last years, PKC has become an attractive target for the treatment of cancer patients given its widely described role in carcinogenesis and tumor promotion. Despite the extensive research conducted on these phorbol ester receptors there is only limited knowledge about the contribution of each individual PKC isozyme in malignant transformation, mainly due to the different roles of each isozyme and their tissue-specificity. This diversity provides the unique opportunity to develop specific pharmacological agents, but the complex nature of the signaling pathways activated by different PKCs challenges selective drug therapies. Currently, several classes of PKC inhibitors including small molecule kinase inhibitors, biologic modulators, and anti-sense oligonucleotides are being evaluated for the treatment of different cancers where PKC isozymes were found to be deregulated as lung, colon, skin, prostate, and breast malignancies. In this article we will review which PKC isoforms are deregulated in different human cancers and summarize the mechanism of action of some of the major PKC modulators, analyzing the strengths and weaknesses of each one in the clinical setting.

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VASCULAR ENDOTHELIAL GROWTH FACTOR INDUCES PROTEIN KINASE C (PKC)‐DEPENDENT Akt/PKB ACTIVATION AND PHOSPHATIDYLINOSITOL 3′‐KINASE‐MEDIATED PKCδ PHOSPHORYLATION: ROLE OF PKC IN ANGIOGENESIS

Cited by 18 publications

References 0 publications

Precision Culture Scaling to Establish High‐Throughput Vasculogenesis Models

Precision Culture Scaling to Establish High‐Throughput Vasculogenesis Models

Role of protein kinase C in arginine vasopressin‐stimulated ERK and p70S6 kinase phosphorylation

The Pros and Cons of Targeting Protein Kinase c (PKC) in the Management of Cancer Patients

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