scholarly journals Interleukin-3-stimulated haemopoietic stem cell proliferation. Evidence for activation of protein kinase C and Na+/H+ exchange without inositol lipid hydrolysis

1988 ◽  
Vol 256 (2) ◽  
pp. 585-592 ◽  
Author(s):  
A D Whetton ◽  
S J Vallance ◽  
P N Monk ◽  
E J Cragoe ◽  
T M Dexter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Intracellular Ph ◽  
Stem Cell Proliferation ◽  
Interleukin 3 ◽  
Haemopoietic Stem Cell ◽  
Kinase C

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.

Activation of protein kinase C delta by ψδRACK peptide promotes embryonic stem cell proliferation through ERK 1/2

2013 ◽  
Vol 94 ◽  
pp. 497-512 ◽  
Author(s):  
Nicole Milaré Garavello ◽  
Darlene Aparecida Pena ◽  
José Matheus Camargo Bonatto ◽  
Mariana Lemos Duarte ◽  
Helio Miranda Costa-Junior ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Protein Kinase C Delta ◽  
Stem Cell Proliferation ◽  
Kinase C

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

2018 ◽  
Vol 51 (1) ◽  
Author(s):  
Dong-Sik Chae ◽  
Chang Youn Lee ◽  
Jiyun Lee ◽  
Hyang-Hee Seo ◽  
Chong-Hyuk Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Adhesion Molecules ◽  
Kinase C

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

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.

Phorbol esters activate protein kinase C and glucose transport and can replace the requirement for growth factor in interleukin-3-dependent multipotent stem cells

1986 ◽  
Vol 84 (1) ◽  
pp. 93-104 ◽  
Author(s):  
A.D. Whetton ◽  
C.M. Heyworth ◽  
T.M. Dexter
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
Glucose Transport ◽  
Hexose Transport ◽  
Cellular Survival ◽  
Interleukin 3 ◽  
Kinase C

Interleukin 3 (IL-3) promotes the survival, proliferation and development of progenitor cells from several distinct haemopoietic lineages and can also stimulate the self-renewal of stem cells. We have explored the mode of action of this growth factor in promoting survival and proliferation, using a multipotent haemopoietic stem cell line FDC-Mix 1. In the absence of IL-3 these cells died within 16–48 h. However, this requirement for IL-3 could be replaced by 12-O-tetradecanoylphorbol-13-acetate (TPA) plus Ca2+ ionophore, which promoted not only survival but also DNA synthesis with no concomitant loss of the multipotential nature of these cells. TPA and Ca2+ ionophore, respectively, could also interact synergistically with IL-3 to promote DNA synthesis. Both IL-3 and TPA stimulated the translocation of protein kinase C (PK-C) from the cytosol to a membrane-bound form in FDC-Mix 1 cells. Previously we suggested that IL-3 can activate the primary metabolism of IL-3-dependent cells so that increased glucose transport and glycolysis lead to maintenance of ATP levels and cellular survival. To investigate whether TPA and, or, Ca2+ ionophore could also influence cellular survival via an activation of glucose uptake we assessed the effects of these agents on hexose transport. TPA +/− Ca2+ ionophore activated hexose transport to the same degree as does IL-3 but these agents cannot superstimulate FDC-Mix 1 hexose transport in cells that already exhibit an activated transport system from preincubation with IL-3. We conclude that IL-3 maintains FDC-Mix 1 cells via its ability to activate PK-C and increase cytosolic levels of Ca2+, and that an IL-3-mediated activation of PK-C may promote cellular survival via its ability to enhance hexose uptake by phosphorylating the glucose transport protein.

scholarly journals Targeting Protein Kinase C in Glioblastoma Treatment

Biomedicines ◽  
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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