Glycogen synthase kinase 3β regulation of nuclear factor of activated T-cells isoform c1 in the vascular smooth muscle cell response to injury

Chow, Winsion; Hou, Guangpei; Bendeck, Michelle P.

doi:10.1016/j.yexcr.2008.07.010

Cited by 25 publications

(19 citation statements)

References 38 publications

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“…Kinase activity and rephosphorylation of NFAT can also influence NFAT localization in ventricular myocytes (4,9,53). When we inhibited the cellular kinases GSK3␤ with 1 mol/l alsterpaullone or JNK2 using 1 mol/l SP-600125 in ventricular cells by incubations overnight, there was a substantial nuclear accumulation of NFATc1, as indicated by an increase in the NFAT nuc -to-NFAT cyt ratio from 2.10 Ϯ 0.08 (control, n ϭ 34) to 4.17 Ϯ 0.32 (SP-600125, n ϭ 20) and 5.28 Ϯ 0.36 (alsterpaullone, n ϭ 24).…”

Section: Pharmacological Manipulation Of Nfatc1 In Cardiac Myocytesmentioning

confidence: 99%

Isoform- and tissue-specific regulation of the Ca²⁺-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Rinne

Kapur

Molkentin

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Nuclear factors of activated T cells (NFATs) are Ca(2+)-sensitive transcription factors that have been implicated in hypertrophy, heart failure (HF), and arrhythmias. Cytosolic NFAT is activated by dephosphorylation by the Ca(2+)-sensitive phosphatase calcineurin, resulting in translocation to the nucleus, which is opposed by kinase activity, rephosphorylation, and nuclear export. Four different NFAT isoforms are expressed in the heart. The activation and regulation of NFAT in adult cardiac myocytes, which may depend on the NFAT isoform and cell type, are not fully understood. This study compared basal localization, import, and export of NFATc1 and NFATc3 in adult atrial and ventricular myocytes to identify isoform- and tissue-specific regulatory mechanisms of NFAT activation under physiological conditions and in HF. NFAT-green fluorescent protein fusion proteins and NFAT immunocytochemistry were used to analyze NFAT regulation in adult cat and rabbit myocytes. NFATc1 displayed basal nuclear localization in atrial and ventricular myocytes, an effect that was attenuated by reducing intracellular Ca(2+) concentration and inhibiting calcineurin, and enhanced by the inhibition of nuclear export. In contrast, NFATc3 was localized to the cytoplasm but could be driven to the nucleus by angiotensin II and endothelin-1 stimulation in atrial, but not ventricular, cells. Inhibition of nuclear export (by leptomycin B) facilitated nuclear localization in both cell types. Ventricular myocytes from HF rabbits showed increased basal nuclear localization of endogenous NFATc3 and reduced responsiveness of NFAT translocation to phenylephrine stimulation. In control myocytes, Ca(2+) overload, leading to spontaneous Ca(2+) waves, induced substantial translocation of NFATc3 to the nucleus. We conclude that the activation of NFAT in adult cardiomyocytes is isoform and tissue specific and is tightly controlled by nuclear export. NFAT is activated in myocytes from HF animals and may be secondary to Ca(2+) overload.

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Section: Pharmacological Manipulation Of Nfatc1 In Cardiac Myocytesmentioning

confidence: 99%

Isoform- and tissue-specific regulation of the Ca²⁺-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Rinne

Kapur

Molkentin

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Dephosphorylation of NFATs, which is mediated by a Ca 2ϩ /calmodulin-dependent phosphatase, calcineurin, leads to their activation and nuclear translocation (14). However, phosphorylation by kinases such as glycogen synthase kinase 3␤ (GSK3␤) invokes their nuclear export and inactivation (15). NFATs bind to the GGAAA core DNA element present in the promoter regions of the genes and influ-ence their transcription.…”

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confidence: 99%

Protein Kinase N1 Is a Novel Substrate of NFATc1-mediated Cyclin D1-CDK6 Activity and Modulates Vascular Smooth Muscle Cell Division and Migration Leading to Inward Blood Vessel Wall Remodeling

Singh

Kundumani‐Sridharan

Kumar

et al. 2012

Journal of Biological Chemistry

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Background:The purpose of this study was to test the role of PKN1 in vascular wall remodeling. Results: PKN1 mediates MCP-1-induced HASMC migration/proliferation and balloon injury-induced neointima formation. Conclusion: PKN1 plays a role in vascular wall remodeling following balloon injury. Significance: PKN1 could be a promising target for the next generation of drugs for vascular diseases such as restenosis.

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“…In our results, LTD 4 particularly increased expression of NFATc1, whereas other NFATs did not display significant changes of expression (data not shown). NFATc1 has been implicated in the migration and proliferation of vascular smooth muscle cell and targeted disruption of NFATc1 results in embryonic lethality [Chow et al, 2008;Nguyen and Di Giovanni, 2008]. In the present study, activation of FAK and/or paxillin was decreased by PI3K/Akt and calcineurin/NFAT inhibitors, which regulate assembly of focal adhesions in migrating cells and participate in transduction pathway informing the nucleus for contact with matrix.…”

Section: Involvement Of Gsk-3b/b-catenin and Nfatc1mentioning

confidence: 49%

Effect of leukotriene D₄ on mouse embryonic stem cell migration and proliferation: Involvement of PI3K/Akt as well as GSK‐3β/β‐catenin signaling pathways

Kim¹,

Lee²,

Kim³

et al. 2010

J of Cellular Biochemistry

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The actual leukotriene D(4) (LTD(4)) signaling pathways that regulate cell proliferation have not been elucidated thoroughly although fatty acid and its metabolites play a key role in regulations of embryonic functions. Thus, this study investigated the response of mouse embryonic stem (ES) cells exposed to LTD(4) and elucidated the signaling pathways as well. LTD(4) increased DNA synthesis in concentration-dependent (≥10(-7) M) and time-dependent (≥12 h) manners, as determined by [(3)H] thymidine incorporation and increased cell number. LTD(4) induced the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and the increase of intracellular Ca(2+) levels via cysteinyl leukotriene (CysLT) 1 and 2 receptors. LTD(4) increased Akt activation and calcineurin expression, which were blocked by STAT3 inhibitor and calcium chelators. LTD(4)-induced glycogen synthase kinase (GSK)-3β phosphorylation was decreased by LY294002, Akt inhibitor, and cyclosporine A. LTD(4) inhibited the phosphorylation of β-catenin. In addition, LTD(4)-stimulated migration through increased activation of focal adhesion kinase (FAK) and paxillin which were blocked by Akt inhibitor and cyclosporine A. LTD(4)-induced increases in protooncogene and cell cycle regulatory proteins were blocked by cyclosporine A, FAK siRNA, and β-catenin siRNA. In conclusion, LTD(4)-stimulated mouse ES cell proliferation and migration via STAT3, phosphoinositide 3-kinases (PI3K)/Akt, Ca(2+)-calcineurin, and GSK-3β/β-catenin pathway.

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Glycogen synthase kinase 3β regulation of nuclear factor of activated T-cells isoform c1 in the vascular smooth muscle cell response to injury

Cited by 25 publications

References 38 publications

Isoform- and tissue-specific regulation of the Ca²⁺-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Isoform- and tissue-specific regulation of the Ca²⁺-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Protein Kinase N1 Is a Novel Substrate of NFATc1-mediated Cyclin D1-CDK6 Activity and Modulates Vascular Smooth Muscle Cell Division and Migration Leading to Inward Blood Vessel Wall Remodeling

Effect of leukotriene D₄ on mouse embryonic stem cell migration and proliferation: Involvement of PI3K/Akt as well as GSK‐3β/β‐catenin signaling pathways

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Glycogen synthase kinase 3β regulation of nuclear factor of activated T-cells isoform c1 in the vascular smooth muscle cell response to injury

Cited by 25 publications

References 38 publications

Isoform- and tissue-specific regulation of the Ca2+-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Isoform- and tissue-specific regulation of the Ca2+-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Protein Kinase N1 Is a Novel Substrate of NFATc1-mediated Cyclin D1-CDK6 Activity and Modulates Vascular Smooth Muscle Cell Division and Migration Leading to Inward Blood Vessel Wall Remodeling

Effect of leukotriene D4 on mouse embryonic stem cell migration and proliferation: Involvement of PI3K/Akt as well as GSK‐3β/β‐catenin signaling pathways

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Isoform- and tissue-specific regulation of the Ca²⁺-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Isoform- and tissue-specific regulation of the Ca²⁺-sensitive transcription factor NFAT in cardiac myocytes and heart failure

Effect of leukotriene D₄ on mouse embryonic stem cell migration and proliferation: Involvement of PI3K/Akt as well as GSK‐3β/β‐catenin signaling pathways