Stress kinase p38 mediates EGFR transactivation by hyperosmolar concentrations of sorbitol

Cheng, Hao; Kartenbeck, Jürgen; Kabsch, Kirsten; Mao, Xiahong; Marques, Margarita M; Alonso, Ángel

doi:10.1002/jcp.10134

Cited by 53 publications

(50 citation statements)

References 52 publications

(57 reference statements)

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“…The alterations within the keratin filament network play a pivotal role in activation of stress kinases (27). Shrinkage of KCs treated with sorbitol has been shown to activate p38 MAPK (28). Mechanical stress of KCs can also activate ERK 1/2, c-Jun, and JNK (27,29).…”

Section: Discussionmentioning

confidence: 99%

Desmoglein Versus Non-desmoglein Signaling in Pemphigus Acantholysis

Chernyavsky

Arredondo

Kitajima

et al. 2007

Journal of Biological Chemistry

128

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Although it is accepted that pemphigus antibody binding to keratinocytes (KCs) evokes an array of intracellular biochemical events resulting in cell detachment and death, the triggering events remain obscure. It has been postulated that the binding of pemphigus vulgaris IgG (PVIgG) to KCs induces "desmosomal" signaling. Because in contrast to integrins and classical cadherins, desmoglein (Dsg) molecules are not known to elicit intracellular signaling, and because PV patients also produce non-Dsg autoantibodies, we investigated the roles of both Dsg and non-desmoglein PV antigens. The time course studies of KCs treated with PVIgG demonstrated that the activity of Src peaked at 30 min, EGF receptor kinase (EGFRK) at 60 min, and p38 MAPK at 240 min. The Src inhibitor PP2 decreased EGFRK and p38 activities by ϳ45 and 30%, respectively, indicating that in addition to Src, PVIgG evokes other triggering events. The shrinkage of KCs (cell volume reduction) became significant at 120 min, keratin aggregation at 240 min, and an increase of TUNEL positivity at 360 min. Pretreatment of KCs with PP2 blocked PVIgG-dependent cell shrinkage and keratin aggregation by ϳ50% and TUNEL positivity by ϳ25%. The p38 MAPK inhibitor PD169316 inhibited these effects by ϳ15, 20, and 70%, respectively. Transfection of KCs with small interfering RNAs that silenced expression of Dsg1 and/or Dsg3 proteins, blocked ϳ50% of p38 MAPK activity but did not significantly alter the PVIgG-dependent rise in Src and EGFRK activities. These results indicate that activation of p38 MAPK is a late signaling step associated with collapse of the cytoskeleton and disassembly of desmosomes caused by upstream events involving Src and EGFRK. Therefore, the early acantholytic events are triggered by non-Dsg antibodies.

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Section: Discussionmentioning

confidence: 99%

Desmoglein Versus Non-desmoglein Signaling in Pemphigus Acantholysis

Chernyavsky

Arredondo

Kitajima

et al. 2007

Journal of Biological Chemistry

128

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“…[19][20][21][22] Thus, we also studied the effect of high osmolality on quiescent, serum-deprived cultures (Fig. 2B).…”

Section: Increased Osmolality Immediately Inhibits Erk and Akt Activamentioning

confidence: 99%

Effect of varying osmotic conditions on the response of bovine nucleus pulposus cells to growth factors and the activation of the ERK and Akt pathways

Mavrogonatou

Kletsas

2010

Journal Orthopaedic Research

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Intervertebral disc and especially nucleus pulposus is characterized by low cellularity. Additionally, extreme variations in osmolality are observed in this tissue, as a result of its specific physicochemical environment, daily activities, or degeneration. In this study, we investigated the role of osmotic fluctuations in the proliferative response of nucleus pulposus cells to exogenous growth factors. In particular, we examined the effect of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) on the proliferation of bovine nucleus pulposus cells and on the activation of the MEK/ERK and PI-3-K/Akt pathways under varying osmotic conditions, in an effort to understand the mechanisms regulating cell proliferation in the intact and the degenerated intervertebral disc. Exposure of cells to high osmolality restrained novel DNA synthesis induced by PDGF or IGF-I in a dose-dependent manner and reduced ERK and Akt activation stimulated by serum or isolated growth factors. Our findings indicate that hyperosmolality imposes a strict control in intervertebral disc cells' proliferation, while hypo-osmotic conditions prevailing in degenerated discs may offer a more permissive environment for cellular proliferation. Keywords: intervertebral disc; growth factor; osmolality; ERK; Akt Back pain represents a major health problem and, although its exact etiology is not yet fully elucidated, it is associated with intervertebral disc degeneration.

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“…UV was previously found to increase intracellular reactive oxygen species, activation of protein kinase C, and p38 (Sarasin, 1999;Cheng et al, 2002), with reaction conditions similar to the hyperosmotic stress reaction. The final target of hypertonia and ultraviolet radiation is DNA, which leads to DNA fracture in cells (Heck et al, 2003).…”

Section: Introductionmentioning

confidence: 84%

Effect of ultraviolet A exposure on transport of compatible organic osmolytes in human lens epithelial cells

2015

Genet. Mol. Res.

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ABSTRACT. Compatible organic osmolytes, such as betaine, myoinositol, and taurine, are involved in antioxidant defense, protein stabilization, and stress responses. This osmolyte strategy requires the expression of specific osmolyte transporters such as betaine (BGT-1), myoinositol (SMIT), and taurine (TAUT). In contrast to the kidney, keratinocytes, and neural cells, few studies have examined osmolytes in human lens epithelial cells (HLECs). We examined the expression of mRNA specific for BGT-1, SMIT, and TAUT in HLECs. In comparison to normoosmotic (305 mOsM) controls, there was a 3-5-fold time-dependent reaction of BGT-1, SMIT, and TAUT mRNA levels in HLECs exposed to hyperosmotic stress (405 mOsM). Maximal responses were obtained for BGT-1, SMIT, and TAUT mRNA expression after 3, 24 and 9 h of hyperosmotic exposure, respectively. This expression was correlated with increased osmolyte uptake. In contrast, hypoosmotic (205 mOsM) stimulation led to a significant efflux of osmolytes. Exposure to ultraviolet A (340-400 nm) radiation significantly stimulated osmolyte uptake. Increased osmolyte uptake was associated with upregulation of mRNA steady-state levels for osmolyte transporters in irradiated cells. These results demonstrate that ultraviolet A radiation leads to the accumulation of compatible organic osmolytes in HLECs as hyperosmotic pressure, which can maintain cellular environmental homeostasis.

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Stress kinase p38 mediates EGFR transactivation by hyperosmolar concentrations of sorbitol

Cited by 53 publications

References 52 publications

Desmoglein Versus Non-desmoglein Signaling in Pemphigus Acantholysis

Desmoglein Versus Non-desmoglein Signaling in Pemphigus Acantholysis

Effect of varying osmotic conditions on the response of bovine nucleus pulposus cells to growth factors and the activation of the ERK and Akt pathways

Effect of ultraviolet A exposure on transport of compatible organic osmolytes in human lens epithelial cells

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