Oxidative Stress and Vanadate Induce Tyrosine Phosphorylation of Phosphoinositide-Dependent Kinase 1 (PDK1)

Prasad, Nagendra; Topping, Robert S.; Zhou, Dongmei; Decker, Stuart J.

doi:10.1021/bi000387i

Cited by 79 publications

(85 citation statements)

References 55 publications

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“…SGK shares a regulatory pathway with Akt. Like Akt, SGK can be activated by PI3K [120][121][122] even though it lacks a PH domain. Secondly, both Akt and SGK are directly phosphorylated and activated by PDK1.…”

Section: Pi3k/akt Signaling and The Bcl-2 Family Of Proteinsmentioning

confidence: 99%

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Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy

et al. 2003

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Section: Pi3k/akt Signaling and The Bcl-2 Family Of Proteinsmentioning

confidence: 99%

“…Secondly, both Akt and SGK are directly phosphorylated and activated by PDK1. 119,122 Interestingly, SGK and Akt phosphorylate different residues of FKHR-L1 and synergistically inactivate B-Raf.…”

Section: Pi3k/akt Signaling and The Bcl-2 Family Of Proteinsmentioning

confidence: 99%

Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy

et al. 2003

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“…To test whether SGK plays a role in B-Raf regulation, we examined B-Raf kinase activity in the presence or absence of SGK. HA-B-Raf was transfected in HEK293 cells with SGK-S422D, which is a constitutively active SGK mutant containing the activation phosphorylation site Ser 422 substituted by an aspartic residue (42). HA-SGK-S422D was used because wild-type SGK has low activity in the absence of serum stimulation.…”

Section: Inhibition Of B-raf By Sgk-mentioning

confidence: 99%

“…Several groups have reported that SGK could also be activated by the PI3K pathway (40,41). PDK1 is likely to directly phosphorylate and enhance SGK activity (41,42). However, physiological targets of SGK are largely unknown.…”

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confidence: 99%

Serum- and Glucocorticoid-inducible Kinase SGK Phosphorylates and Negatively Regulates B-Raf

Zhang¹,

Tang²,

Zhu³

et al. 2001

Journal of Biological Chemistry

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Phosphorylation can both positively and negatively regulate activity of the Raf kinases. Akt has been shown to phosphorylate and inhibit C-Raf activity. We have recently reported that Akt negatively regulates B-Raf kinase activation by phosphorylating multiple residues within its amino-terminal regulatory domain. Here we investigated the regulation of B-Raf by serum and glucocorticoid-inducible kinase, SGK, which shares close sequence identity with the catalytic domain of Akt but lacks the pleckstrin homology domain. We observed that SGK inhibits B-Raf activity. A comparison of substrate specificity between SGK and Akt indicates that SGK is a potent negative regulator of B-Raf. In contrast to Akt, SGK negatively regulates B-Raf kinase activity by phosphorylating only a single Akt consensus site, Ser 364 . Under similar experimental conditions, SGK displays a measurably stronger inhibitory effect on B-Raf kinase activity than Akt, whereas Akt exhibits a more inhibitory effect on the forkhead transcription factor, FKHR. The selective substrate specificity is correlated with an enhanced association between Akt or SGK and their preferred substrates, FKHR and B-Raf, respectively. These results indicate that B-Raf kinase activity is negatively regulated by Akt and SGK, suggesting that the cross-talk between the B-Raf and other signaling pathways can be mediated by both Akt and SGK.

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“…Oxidative stress is intrinsically associated with a state of increased turnover of biomolecules induced by elevated rates of reactive oxygen species. However, extensive studies have recently demonstrated that other proteins also increase their activity upon oxidative stress in a significant manner, for example c-Jun NH 2 -terminal kinase (49), p70-S6 kinase (50), Akt/PKB (51), glucose-6-phosphate dehydrogenase (52), PDK1 (53), and SGK (54), among many other examples. Interestingly, the last two proteins are related to the mineralocorticoid biological response.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Mineralocorticoid Receptor (MR)-dependent Biological Response by Oxidative Stress and Aging

Piwien-Pilipuk

Ayala

Machado

et al. 2002

Journal of Biological Chemistry

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Acute and chronic treatments of mice with the glutathione-depleting agent, L-buthionine-(SR)-sulfoximine (BSO), impaired the mineralocorticoid receptor (MR)-dependent biological response by inhibiting aldosterone binding. This steroid-binding inhibition was fully reversed when reducing agents were added to kidney cytosol obtained from mice treated for 5 h, but it was only partially reversed in cytosol obtained from mice treated for 10 days. Although the oligomeric structure of the MR-hsp90 heterocomplex was always unaffected, a decreased amount of MR protein was evidenced after the long term treatment. Such a deleterious effect was correlated with a post-translational modification of MR, as demonstrated by an increased level of receptor carbonylation. In addition, a failure at the elongation/termination step was also observed during the receptor translation process in a reticulocyte lysate system. Thus, a high polyribosomes/monomers ratio and both increased proteolysis and decreased ADP-ribosylatable concentration of elongation factor 2 (EF-2) were shown. Importantly, similar observations were also performed in vivo after depletion of glutathione. Notwithstanding the EF-2 functional disruption, not all renal proteins were equally affected as the MR. Interestingly, both EF-2 and MR expressed in old mice were similarly affected as in L-buthionine-(SR)-sulfoximine-treated young mice. We therefore propose that a dramatic depletion of glutathione in kidney cells mimics the cumulative effect of aging which, at the end, may lead to a renal mineralocorticoid dysfunction.The biological effects of aldosterone (ALDO) 1 are mediated by the mineralocorticoid receptor (MR), a ligand-dependent transcription factor that belongs to the steroid receptor class of nuclear receptors. The transcriptional activation of the MR in epithelial cells triggers a series of events that are responsible for the regulation of the internal medium, i.e. Na ϩ and H 2 O retention and K ϩ and H ϩ elimination. Steroid receptors exist as nuclear or cytoplasmic heterocomplexes associated to the 90-kDa heat shock protein (hsp90) chaperone system (1, 2). Regardless of its subcellular localization, this association stabilizes the receptor in its hormone binding and transcriptionally inactive form. It is thought that upon ligand binding, the steroid receptors undergo a conformational change that leads to the dissociation of the hsp90-heterocomplex, dephosphorylation, dimerization, translocation into the nucleus (for cytoplasmic receptors), hyperphosphorylation, and binding to specific hormone-responsive elements. Nonetheless, the actual temporal sequence of this cascade of events remains unclear. In contradiction to what was previously thought, it has been shown that the dissociation of the hsp90-heterocomplex upon steroid binding is not necessarily the first step in the signaling pathway (3, 4). Consistent with this observation, it has also been postulated that the receptorhsp90 complex requires intact cytoskeletal tracks to move efficiently toward the n...

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Oxidative Stress and Vanadate Induce Tyrosine Phosphorylation of Phosphoinositide-Dependent Kinase 1 (PDK1)

Cited by 79 publications

References 55 publications

Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy

Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy

Serum- and Glucocorticoid-inducible Kinase SGK Phosphorylates and Negatively Regulates B-Raf

Impairment of Mineralocorticoid Receptor (MR)-dependent Biological Response by Oxidative Stress and Aging

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