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

Leskow, Federico Coluccio; Krasnapolski, Martín; Urtreger, Alejandro J.

doi:10.2174/138920111798376950

Cited by 12 publications

(5 citation statements)

References 108 publications

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“…The first ATP-binding site inhibitor, staurosporine, was developed over 30 years ago. This compound binds to all PKC isozymes but also binds non-specifically to several other serine/threonine kinases [ 139 ]. Midostaurin (PKC412), a derivative of staurosporine, was subsequently developed in an attempt to design a more isozyme specific ATP-binding site inhibitor.…”

Section: Consequences Of Targeting Pkcmentioning

confidence: 99%

Targeting Protein Kinase C Downstream of Growth Factor and Adhesion Signalling

Dowling¹,

Kiely²

2015

Cancers

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The signaling outputs of Receptor Tyrosine Kinases, G-protein coupled receptors and integrins converge to mediate key cell process such as cell adhesion, cell migration, cell invasion and cell proliferation. Once activated by their ligands, these cell surface proteins recruit and direct a diverse range of proteins to disseminate the appropriate response downstream of the specific environmental cues. One of the key groups of proteins required to regulate these activities is the family of serine/threonine intracellular kinases called Protein Kinase Cs. The activity and subcellular location of PKCs are mediated by a series of tightly regulated events and is dependent on several posttranslational modifications and the availability of second messengers. Protein Kinase Cs exhibit both pro- and anti-tumorigenic effects making them an interesting target for anti-cancer treatment.

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Section: Consequences Of Targeting Pkcmentioning

confidence: 99%

Targeting Protein Kinase C Downstream of Growth Factor and Adhesion Signalling

Dowling¹,

Kiely²

2015

Cancers

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“…Moreover, PKCs have been studied as targets for the treatment of cancer for many years. The benefits of using PKC inhibitors to control cancer have been discussed elsewhere (11, 12).…”

Section: Pkc and Cancermentioning

confidence: 99%

“…The atypical PKC isozymes are structurally and functionally distinct from other PKCs because they lack the calcium‐, phospholipid‐, and DAG‐binding motifs (12). It has been described that atypical PKC activity can be regulated by 3‐phosphoinositides (64) and by phosphoinositide‐dependent kinase 1 (PDK1) phosphorylation (65).…”

Section: Pkc and Breast Cancermentioning

confidence: 99%

Contribution of individual PKC isoforms to breast cancer progression

2011

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SummaryThe protein kinase C (PKC) family of serine/threonine kinases has been intensively studied in cancer since their discovery as major receptors for the tumor-promoting phorbol esters. The contribution of each individual PKC isozyme to malignant transformation is only partially understood, but it is clear that each PKC plays different role in cancer progression. PKC deregulation is a common phenomenon observed in breast cancer, and PKC expression and localization are usually dynamically regulated during mammary gland differentiation and involution. In fact, the overexpression of several PKCs has been reported in malignant human breast tissue and breast cancer cell lines. In this review, we summarize the knowledge available on the specific roles of PKC isoforms in the development, progression, and metastatic dissemination of mammary cancer. We also discuss the role of PKC isoforms as therapeutic targets, and their potential as markers for prognosis or treatment response.

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“…Malfunctions in enzymes that produce ADP, such as kinases, ATPases, DNA helicases, etc., can have serious health consequences . Many of these enzymes are attractive drug targets and of great interest to both academics and industry . A few examples of QD based ADP assays are available, though ATP assays are much more common. − The sensor is based on an ADP recognition agent, for example, an antibody (Ab) or aptamer.…”

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confidence: 99%

Quantum Dots as Förster Resonance Energy Transfer Acceptors of Lanthanides in Time-Resolved Bioassays

Dı́az¹,

Lasarte‐Aragonés

Lowery

et al. 2018

ACS Appl. Nano Mater.

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We report a flexible and modular design for biosensors based on exploiting semiconductor quantum dots (QDs) and their excellent Forster resonance energy transfer (FRET) acceptor properties along with the long-lived fluorescent lifetimes of lanthanide donors. We demonstrate the format's wide application by developing a broad adenosine diphosphate (ADP) sensor with quantitative and highthroughput capabilities as a kinase/ATPase assay method. The sensor is based on a Terbium (Tb)-labeled antibody (Ab) that selectively recognizes ADP versus ATP. The Tb-labeled Ab (Ab-Tb) acts as a FRET donor to a QD, which has an ADP modified His 6 -peptide conjugated to its surface via metal-affinity coordination. This strategy of using self-assembly, modified peptides to present antibody epitopes on QD surfaces is readily transferable to other assays of interest. We utilize time-resolved FRET (TR-FRET) to measure the amounts of Ab-Tb bound to the QD by looking at the emission ratio of the QD and Tb in a time-gated manner, minimizing background signal. With the addition of free ADP the antibody is competitively separated from the QD and a change in the ratiometric emission signal correlates with the free ADP concentration. The sensor obtained a detection limit below 10 nM of free ADP and quantitation limit of 35 nM ADP using 8 nM of sensor. Quantitative values were obtained for a model enzyme (glucokinase) kinetics, as well as demonstrations of the assays capability to distinguish enzyme inhibitors. We discuss future outlooks and note areas for improvement in similar design strategies.

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

Cited by 12 publications

References 108 publications

Targeting Protein Kinase C Downstream of Growth Factor and Adhesion Signalling

Targeting Protein Kinase C Downstream of Growth Factor and Adhesion Signalling

Contribution of individual PKC isoforms to breast cancer progression

Quantum Dots as Förster Resonance Energy Transfer Acceptors of Lanthanides in Time-Resolved Bioassays

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