Priming stem cells with protein kinase C activator enhances early stem cell-chondrocyte interaction by increasing adhesion molecules

Interleukin 3 (IL-3) is an important regulator of haemopoietic stem cell proliferation both in vivo and in vitro. Little is known about the possible mechanisms whereby this growth factor acts on stem cells to stimulate cell survival and proliferation. Here we have investigated the role of intracellular pH and the Na+/H+ antiport in stem cell proliferation using the multipotential IL-3-dependent stem cell line, FDCP-Mix 1. Evidence is presented that IL-3 can stimulate the activation of an amiloride-sensitive Na+/H+ exchange via protein kinase C activation. IL-3-mediated activation of the Na+/H+ exchange is not observed in FDCP-Mix 1 cells where protein kinase C levels have been down-modulated by treatment with phorbol esters. Also the protein kinase C inhibitor H7 can inhibit IL-3-mediated increases in intracellular pH. This activation of Na+/H+ exchange via protein kinase C has been shown to occur with no measurable effects of IL-3 on inositol lipid hydrolysis or on cytosolic Ca2+ levels. Evidence is also presented that this IL-3-stimulated alkalinization acts as a signal for cellular proliferation in stem cells.

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Cullin3 promotes stem cell progeny differentiation by facilitating aPKC-directed asymmetric Numb localization

10.1101/2020.07.29.227603 ◽

2020 ◽

Author(s):

Hideyuki Komori ◽

Noemi Rives-Quinto ◽

Xu Han ◽

Lucas Anhezini ◽

Ari J. Esrig ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Protein Kinase C ◽

Protein Kinase ◽

Cell Fate ◽

Kinase Activity ◽

Cell Fate Decisions ◽

Kinase C ◽

Cullin 3 ◽

Cortical Localization

SummaryAsymmetric segregation of Numb is a conserved mechanism for regulating Notch-mediated binary cell fate decisions; however, the mechanisms controlling Numb segregation remain unclear. Previous studies have proposed an “exclusion” model, suggesting that atypical protein kinase C (aPKC) negatively regulates Numb cortical localization. Here, we report that aPKC kinase activity positively promotes basal cortical Numb localization during asymmetric division of Drosophila neural stem cells (neuroblasts) and that Cullin 3 (Cul3) is required for aPKC-directed basal Numb localization. In numb- or cul3-mutant brains, decreased levels of Numb segregated into neuroblast progeny failed to downregulate Notch, leading to supernumerary neuroblast formation. Increased aPKC kinase activity suppressed supernumerary neuroblast formation by concentrating residual Numb protein at the basal cortex and in neuroblast progeny, whereas decreased aPKC function enhanced the supernumerary neuroblast phenotype by reducing basal Numb levels. We propose that aPKC and Cul3 promote basal Numb localization, which is required to downregulate Notch signaling and promote differentiation in neuroblast progeny.

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Faculty Opinions recommendation of Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718106805.793488943 ◽

2013 ◽

Author(s):

Avri Ben-Ze'ev

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Cancer Stem Cells ◽

Therapeutic Target ◽

Breast Cancer Stem Cells ◽

Kinase C

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Targeting Protein Kinase C in Glioblastoma Treatment

Biomedicines ◽

10.3390/biomedicines9040381 ◽

2021 ◽

Vol 9 (4) ◽

pp. 381

Author(s):

Noelia Geribaldi-Doldán ◽

Irati Hervás-Corpión ◽

Ricardo Gómez-Oliva ◽

Samuel Domínguez-García ◽

Félix A. Ruiz ◽

...

Keyword(s):

Stem Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Combined Treatment ◽

Primary Brain Tumor ◽

Kinase C ◽

Pkc Isozymes ◽

New Generation ◽

Effective Drugs

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.

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