C‐kit mutations and PKC crosstalks: PKC translocates to nucleous only in cells HMC<sup>560,816</sup>

Tobío, Araceli; Alfonso, Amparo; Botana, Luís M.

doi:10.1002/jcb.23191

Cited by 8 publications

(8 citation statements)

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“…In the HMC-1 560 cell line, long-term PKC activation does not induce a decrease neither on cPKCs nor PKCd cytosolic levels. This observation is in accordance with a previous study in which PKC was only activated for 10 min and no modifications on cPKC levels were observed [25]. Surprisingly, PMA treatment induces plasma membrane cPKCs translocation in the HMC-1 560,816 cell line.…”

Section: Discussionsupporting

confidence: 94%

“…However, PKC activation for (18 h) induces a complete absence of degranulation and the absence of cytosolic PKC is observed, which is in accordance with the present results [52]. The opposite effect of PKC activation in cPKC and PKCd cytosolic expression in both cellular lines can explain the contrary effect on the cellular activation, quantified as histamine release, previously described [25,31].…”

Section: Discussionsupporting

confidence: 94%

“…Therefore, nuclear PKCd levels are increased after STI571 treatment in HMC-1 560 cells. Nuclear cPKC levels were not analyzed since in a previous paper we have demonstrated that cPKC isoforms do not translocate to the nucleus [25].…”

Section: Resultsmentioning

confidence: 99%

“…For example, classical PKCs translocate to the membrane in response to an antigen stimulus in RBL-2H3 mast cell line [22,23]. However, PKC can translocates also to the nucleus depending on the stimulus [24,25]. In fact, PKC localization in the nucleus is usually associated with a role on apoptotic cell death, since PKC has been associated with this process and subsequently with caspases activation in several cellular types, including MCs [26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 96%

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Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Tobío

Alfonso

Botana

2015

Cellular Immunology

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The c-kit inhibitor STI571 represents one of the most important treatments for patients with mastocytosis. However, intracellular pathways modulated by this compound are not completely defined. Here, STI571 effect on Protein Kinase C (PKC) regulation is determined in HMC-1 mast cell lines. STI571 activates PKCδ isoform resulting in HMC-1(560) apoptosis. The apoptosis observed is PKCδ-dependent, since PKCδ-silencing avoids STI571 effect. c-kit inhibition implies nuclear PKCδ translocation characterized by a clear dependence on actin cytoskeleton integrity in HMC-1(560) cell line, but not in HMC-1(560,816). Therefore, PKCδ modulations can lead to a serious decrease in STI571 treatment-effectiveness.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Tobío

Alfonso

Botana

2015

Cellular Immunology

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“…The chemiluminiscent signal was detected with the diversity GeneSnap software and analyzed by the diversity 4 gel documentation and analysis system. Relative protein expression was calculated in relation to b-actin expression for each experiment in cytosolic fraction and with histone 1 in nuclear fraction (Tobío et al, 2011). Experiments were carried out at least three times by duplicate.…”

Section: Western Blotting Analysismentioning

confidence: 99%

Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin

Fernández-Araujo¹,

Alfonso²,

Vieytes³

et al. 2015

Toxicology

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Understanding the mechanism of action of the yessotoxin (YTX) is crucial since this drug has potential pharmacological effects in allergic processes, tumor proliferation and neurodegenerative diseases. It has been described that YTX activates apoptosis after 24h of treatment, while after 48 h of incubation with the toxin a decrease in cell viability corresponding to cellular differentiation or non-apoptotic cell death was observed. In this paper, these processes were extensively studied by using the erythroleukemia K-562 cell line. On one hand, events of K-562 cell differentiation into erythrocytes after YTX treatment were studied using hemin as positive control of cell differentiation. Cell differentiation was studied through the cyclic nucleotide response element binding (phospho-CREB) and the transferrin receptor (TfR) expression. On the other hand, using rapamycin as positive control, autophagic hallmarks, as non-apoptotic cell death, were studied after toxin exposure. In this case, the mechanistic target of rapamycin (mTOR) and light chain 3B (LC3B) levels were measured to check autophagy activation. The results showed that cell differentiation was not occurring after 48 h of toxin incubation while at this time the autophagy was triggered. Furthermore after 24h of toxin treatment none of these processes were activated. In addition, the role of the type 4A phosphodiesterase (PDE4A), the intracellular target of YTX, was checked. PDE4A-silencing experiments showed different regulation steps of PDE4A in the autophagic processes triggered either by traditional compounds or YTX. In summary, after 48 h YTX treatment PDE4A-dependent autophagy, as non-apoptotic programmed cell death, is activated.

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Different Role of cAMP Pathway on the Human Mast Cells HMC‐1⁵⁶⁰ and HMC‐1^560,816 Activation

Barreiro-Costa¹,

Tobío²,

Alfonso³

et al. 2014

J of Cellular Biochemistry

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HMC-1 are inflammatory cells that release vasoactive substances such as histamine. These cells have the c-kit receptor permanently activated in the membrane due to mutations in the proto-oncogene c-kit: Val-560 → Gly and Asp-816 → Val. Thus, there are two known cellular lines: HMC-1(560) and HMC-1(560,816) . These mutations are involved in a disease called mastocitosys. In the present paper both lines were used to study the influence of cAMP/PKA/PDEs pathway on the histamine release and Ca(2+) signaling since this pathway is often involved in these process. For this, the cells were preincubated with cAMP/PKA/PDEs modulators such as dibutyryl cAMP (dbcAMP), forskolin, H89, rolipram, IBMX, or imidazole and then stimulated with ionomycin. When cells were stimulated with agents that increase cAMP levels, the histamine release was not modified in HMC-1(560) but decreased in HMC-1(560,816) cells. The same happened when PKA was blocked. Furthermore, PDEs role on histamine release was independent of cAMP in HMC-1(560) cells and possibly also in HMC-1(560,816) cells. By contrast, the modulation of PKA and PDEs together changed the response in both cellular lines, therefore a relationship between them was suggested. All these modulatory effects on histamine release are Ca(2+) -independent. On the other hand, the effect of c-kit modulation on the cAMP/PKA/PDEs pathway was also checked. This receptor was blocked with STI571 (imatinib) and BMS-354825 (dasatinib), but only the last one caused a decrease in the cellular response to ionomycin. This article demonstrates for the first time than the cAMP/PKA/PDEs pathway is involved in the activation of HMC-1(560) and HMC-1(560,816) cells.

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C‐kit mutations and PKC crosstalks: PKC translocates to nucleous only in cells HMC^560,816

Cited by 8 publications

References 38 publications

Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin

Different Role of cAMP Pathway on the Human Mast Cells HMC‐1⁵⁶⁰ and HMC‐1^560,816 Activation

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C‐kit mutations and PKC crosstalks: PKC translocates to nucleous only in cells HMC560,816

Cited by 8 publications

References 38 publications

Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin

Different Role of cAMP Pathway on the Human Mast Cells HMC‐1560 and HMC‐1560,816 Activation

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C‐kit mutations and PKC crosstalks: PKC translocates to nucleous only in cells HMC^560,816

Different Role of cAMP Pathway on the Human Mast Cells HMC‐1⁵⁶⁰ and HMC‐1^560,816 Activation