Glycogen synthase kinase-3 acts upstream of ADP-ribosylation factor 6 and Rac1 to regulate epithelial cell migration

Farooqui, Rizwan; Zhu, Shoutian; Fenteany, Gabriel

doi:10.1016/j.yexcr.2006.01.018

Cited by 42 publications

(48 citation statements)

References 44 publications

(88 reference statements)

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“…44 Other cell signaling genes that are highly expressed in the SOD3 Ϫ/Ϫ lungs include the FGF receptor 3, which has been implicated in lymphatic vessel development 52 ; the Ras effector family member Rassf3, which can function as a tumor suppressor 53 ; and ARf3, a member of the small G-protein family that is involved in epithelial cell proliferation. 54 The extracellular matrix encoding mRNAs, utrophin, and Ndst were also increased in the SOD3 Ϫ/Ϫ mice compared to the other animals. Of particular interest, CD59, a surface protein that conveys resistance to compliment attack, was up-regulated about threefold in mice with embryonic deletion of ecSOD.…”

Section: Discussionmentioning

confidence: 91%

Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air

Góngora

Lob

Landmesser

et al. 2008

The American Journal of Pathology

115

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The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3 ؊/؊ mice compared with either mice with acute SOD3 reduction or wildtype controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe

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Section: Discussionmentioning

confidence: 91%

Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air

Góngora

Lob

Landmesser

et al. 2008

The American Journal of Pathology

115

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“…Conversely, activation of GSK3 causes growth cone collapse in response to semaphorin stimulation in neurites [6], an effect likely related to phosphorylation by GSK3 of the microtubule-associated proteins CRMP2 [30,31] and MAP1B [32], indicating that in contrast to local inhibition, local activation of GSK3 blocks the migratory process by controlling microtubule networks. As opposed to local regulation, inhibition of total cellular GSK3 prevented migration of epithelial cells [33] and extension of lamellipodia in keratinocytes [34] and filopodia in neurons [32]. Thus, a selectively inactivated compartment of GSK3 is spatially localized at protrusions and the leading edge of migrating cells to allow movement, but complete inhibition of cellular GSK3 inhibits these events.…”

Section: Inflammation and Migration: Regulation By Gsk3mentioning

confidence: 98%

Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

2006

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Deciphering what governs inflammation and its effects on tissues is vital for understanding many pathologies. The recent discovery that glycogen synthase kinase-3 (GSK3) promotes inflammation reveals a new component of its well-documented actions in several prevalent diseases which involve inflammation, including mood disorders, Alzheimer's disease, diabetes, and cancer. Involvement in such disparate conditions stems from the widespread influences of GSK3 on many cellular functions, with this review focusing on its regulation of inflammatory processes. GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation, while GSK3 inhibition provides protection from inflammatory conditions in animal models. The involvement of GSK3 and inflammation in these diseases are highlighted. Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions.

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“…The resulting immunoprecipitates were washed three times in kinase assay wash buffer (20 mM HEPES, 20 mM ␤-glycerophosphate, and 1 mM EDTA at pH 7.5) and then resuspended in 35 l of kinase assay mixture containing 4 mM MOPS, 2.5 mM ␤-glycerophosphate, 1 mM EGTA, 0.4 mM EDTA, 4 mM MgCl 2 , 0.05 mM dithiothreitol, 40 ng/l BSA, 50 M ATP, 2.5 M cAMP-dependent protein kinase inhibitor peptide (IP 20 ), and 100 M [␥-…”

Section: Gsk3␤-mediated Bax Serinementioning

confidence: 99%

GSK3β Promotes Apoptosis after Renal Ischemic Injury

Wang¹,

Havasi²,

Gall³

et al. 2010

Journal of the American Society of Nephrology

103

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The mechanism by which the serine-threonine kinase glycogen synthase kinase-3␤ (GSK3␤) affects survival of renal epithelial cells after acute stress is unknown. Using in vitro and in vivo models, we tested the hypothesis that GSK3␤ promotes Bax-mediated apoptosis, contributing to tubular injury and organ dysfunction after acute renal ischemia. Exposure of renal epithelial cells to metabolic stress activated GSK3␤, Bax, and caspase 3 and induced apoptosis. Expression of a constitutively active GSK3␤ mutant activated Bax and decreased cell survival after metabolic stress. In contrast, pharmacologic inhibition (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione [TDZD-8]) or RNA interference-mediated knockdown of GSK3␤ promoted cell survival. Furthermore, RNA interference-mediated knockdown of Bax abrogated the cell death induced by constitutively active GSK3␤. In a cell-free assay, TDZD-8 inhibited the phosphorylation of a peptide containing the Bax serine 163 site targeted by stress-activated GSK3␤. In rats, TDZD-8 inhibited ischemia-induced activation of GSK3␤, Bax, and caspase 3; ameliorated tubular and epithelial cell damage; and significantly protected renal function. Taken together, GSK3␤-mediated Bax activation induces apoptosis and tubular damage that contribute to acute ischemic kidney injury.

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Glycogen synthase kinase-3 acts upstream of ADP-ribosylation factor 6 and Rac1 to regulate epithelial cell migration

Cited by 42 publications

References 44 publications

Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air

Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air

Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

GSK3β Promotes Apoptosis after Renal Ischemic Injury

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