Sublethal Levels of Oxidant Stress Stimulate Multiple Serine/Threonine Kinases and Suppress Protein Phosphatases in Jurkat T Cells

Whisler, Ronald L.; Goyette, M.A.; Grants, Iveta; Newhouse, Yvonne G.

doi:10.1006/abbi.1995.1263

Cited by 178 publications

(104 citation statements)

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“…The fact that the PTK inhibitor tyrphostin A23 (20 /.tM) also reduced this response indicates that this effect of H202 is dependent on the activation of both PKC and PTK. The interpretation of these results is consistent with previous work performed in this [9,10] as well as in other [8,11,12] laboratories demonstrating that H~O2 efficiently stimulates PKC and PTK.…”

Section: Resultssupporting

confidence: 93%

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The phosphorylation state of MAP‐kinases modulates the cytotoxic response of smooth muscle cells to hydrogen peroxide

et al. 1996

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Section: Resultssupporting

confidence: 93%

“…In particular, it was reported that the oxidant stimulates proto-oncogene expression [6,7] and activates PKC [8][9][10], PTK [11,12], protein phosphatases [12,13], MAP-kinases [14,15] as well as transcriptional activator proteins (e.g. NF-kB and AP-1) [9,16,17].…”

Section: Introductionmentioning

confidence: 99%

The phosphorylation state of MAP‐kinases modulates the cytotoxic response of smooth muscle cells to hydrogen peroxide

et al. 1996

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“…This would be compatible with the inactivation of PTPs by oxidants (9,52). Although it is not clear which molecule absorbs UV to then cause the generation of a reactive intermediate, the molecular target attacked by this intermediate could well be a cysteine present in the active centers of all PTPs.…”

Section: Discussionmentioning

confidence: 90%

Inactivation of Protein-tyrosine Phosphatases as Mechanism of UV-induced Signal Transduction

Gross¹,

Knebel²,

Tenev³

et al. 1999

Journal of Biological Chemistry

153

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UV irradiation of cells causes ligand-independent acChanges in gene expression are induced by extracellular stimuli most of which are perceived by cell surface receptors. One major class of surface receptors, receptor tyrosine kinases, are primed to react to specific growth factors. Upon ligand binding, the receptor subunits mutually phosphorylate each other. The phosphorylated tyrosine peptide motifs then become docking sites for numerous proteins of the signal transduction network. Most data are compatible with the idea that the ligand triggers this activity of receptor tyrosine kinase by stabilizing the association of subunits (1, 2).In addition to physiologic stimuli, many adverse agents such as carcinogens, metal toxins, oxidants, and radiation can induce signal transduction cascades and changes in gene expression. Ultraviolet (UV) 1 radiation of various wavelength has received most attention. The response to UV appears to depend on several primary radiation target molecules (3, 4). Interestingly, part of the immediate response to UV is mediated by the ligand-independent activation of growth factor receptors (5-7). For instance, the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR) are autophosphorylated within seconds of UV irradiation of cells in culture. The autophosphorylation appears to lead to fully functional receptor signaling, best shown for the EGFR (5, 8 -10) and the insulin receptor (6). Several components of signal transduction, Grb-2, phospholipase C-␥, and Shc that contain SH2 domains or phosphotyrosine-binding domains associate with the receptors in UV-irradiated cells. In consequence, Ras and the Ras-dependent signal transduction pathway to Erk and several other signaling pathways (11) are activated. From the successful activation by UV of receptor heterodimers the conclusion has been derived that a substantial fraction of the receptor tyrosine kinases are in dimer configuration in the absence of ligand and prior to the UV stimulus (Ref. 12, and references therein).How can an unspecific agent such as UV lead to a gain of function: up-regulation of enzymatic activity of the receptors? One suggestion has been, that UV causes cross-links of associated receptor monomers. The dose of UV that would be needed to substantially cross-link proteins, is, however, at least 1 order of magnitude higher than that efficiently activating the receptors. Clustering has, however, been observed for the tumor necrosis factor receptor after UV irradiation (7). It is not clear whether the clustering represents the primary event or whether it is the result rather than the cause of activation. An alternative suggestion has been derived from comparative studies of the kinetics of receptor dephosphorylation with or without UV irradiation (9). UV strongly retards dephosphorylation of both, EGFR and PDGFR. In vitro, irradiation of a plasma membrane vesicle preparation containing phosphatase inactivated the enzymatic activity, compatible with the idea that specific receptor-...

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“…Hyperoxia Decreases PP2A and MKP-3 Activity for ERK Dephosphorylation-It is known that oxidant stimuli, such as hydrogen peroxide, decrease activity of some phosphatases, resulting in ERK activation (29,42,43 2 ) for 24 h. Immunoprecipitation was performed by incubation of the whole cell lysates with antibodies for PP2A or MKP-3. Immunoprecipitated PP2A or MKP-3 was incubated with recombinant pERK in phosphatase buffer at 37°C for 20 min.…”

Section: Hyperoxia-induced Erk Activation Is Not Associated With Incrmentioning

confidence: 99%

Macrophages Survive Hyperoxia via Prolonged ERK Activation Due to Phosphatase Down-regulation

Nyunoya

Monick

Powers

et al. 2005

Journal of Biological Chemistry

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Macrophages exposed to hyperoxia in the lung continue to survive for prolonged periods. We previously reported (Nyunoya, T., Powers, L. S., Yarovinsky, T. O., Butler, N. S., Monick, M. M., and Hunninghake, G. W. (2003) J. Biol. Chem. 278, 36099 -36106) that hyperoxia induces cell cycle arrest and sustained extracellular signal-related kinase (ERK) activity in macrophages. In this study, we determined the mechanisms of hyperoxiainduced ERK activation and how ERK activity plays a pro-survival role in hyperoxia-exposed cells. Inhibition of ERK activity decreased survival of hyperoxia-exposed macrophages. This was due, at least in part, to down-regulation of the pro-apoptotic Bcl-2 family member, BimEL. In determining the mechanism of ERK activation by hyperoxia, we found that ERK activation was not associated with hyperoxia-induced activation of the upstream ERK kinase mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2. When we examined the ability of whole cell lysates from hyperoxia-exposed cells to dephosphorylate purified phosphorylated ERK, we found decreased ERK-directed phosphatase activity. Two particular ERK-directed phosphatases (protein phosphatase 2A and MAPK phosphatase-3) demonstrated decreased activity in hyperoxia-exposed cells. Moreover, whole cell lysates from normoxia-exposed cells depleted of PP2A or MAPK phosphatase-3 were also less able to dephosphorylate ERK. These data demonstrate that, in hyperoxia-exposed macrophages, sustained activation of ERK due to phosphatase down-regulation permits macrophage survival via effects on the balance between pro-and antiapoptotic Bcl-2 family proteins.

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Sublethal Levels of Oxidant Stress Stimulate Multiple Serine/Threonine Kinases and Suppress Protein Phosphatases in Jurkat T Cells

Cited by 178 publications

References 0 publications

The phosphorylation state of MAP‐kinases modulates the cytotoxic response of smooth muscle cells to hydrogen peroxide

The phosphorylation state of MAP‐kinases modulates the cytotoxic response of smooth muscle cells to hydrogen peroxide

Inactivation of Protein-tyrosine Phosphatases as Mechanism of UV-induced Signal Transduction

Macrophages Survive Hyperoxia via Prolonged ERK Activation Due to Phosphatase Down-regulation

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