The Cyclosporin A-sensitive Nuclear Factor of Activated T Cells (NFAT) Proteins Are Expressed in Vascular Smooth Muscle Cells

Boss, Valerie; Abbott, Karen L.; Wang, Xiaofei; Pavlath, Grace K.; Murphy, Thomas J.

doi:10.1074/jbc.273.31.19664

Cited by 94 publications

(41 citation statements)

References 42 publications

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“…NFAT expression or NFAT-derived transactivation has also been described in several types of nonlymphoid cells, including mast cells (34), endothetial cells (35), neuronal cells (36), vascular smooth muscle cells (37), and liver-derived Chang (CHL) cells (38). In this study, we found that exposure of epidermal cells or mouse skin to UV radiation resulted in marked activation of NFAT-dependent transcription.…”

Section: Discussionmentioning

confidence: 53%

“…It is also reported that phosphorylation of NFAT is regulated by several protein kinases, including glycogen synthase kinase 3 and c-Jun NH 2 -terminal kinase 2 (5, 40 -42). With the exception of antigen receptor on lymphocytes, there are only a few reports regarding NFAT activation induced by PDGF and hepatitis B virus x protein in vascular smooth muscle cells and liver-derived CHL cells, respectively (37,38). Also, little is known about regulation and signaling of NFAT activation in skin.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Nuclear Factor of Activated T Cells Activation in UV Response

Huang

Mattjus

et al. 2000

Journal of Biological Chemistry

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Mammalian cells respond to UV radiation by signaling cascades leading to activation of transcription factors, such as activated protein 1, NFB, and p53, a process known as the "UV response." Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immune response and subsequently found to be expressed in other tissues and cells. To date, however, the regulation and function of NFAT in tissues and cells, other than the immune system, are not well understood. In this study, we demonstrate that UV radiation activates NFAT-dependent transcription through a calcium-dependent mechanism in mouse epidermal JB6 cell lines, as well as in the skin of NFAT-luciferase reporter transgenic mice. Exposure of JB6 cells to UV radiation leads to the transactivation of NFAT in a dosedependent manner. A23187 had a synergistic effect with UV for NFAT induction, whereas pretreatment of cells with nifedipine, a calcium channel blocker, dramatically impaired the NFAT activity induced by either UV or UV plus A23187. Calcium-dependent activation of NFAT by UV was further confirmed by an in vivo study using NFAT-luciferase reporter transgenic mice. These results demonstrated that UV radiation is a strong activator for skin NFAT transactivation through calciumdependent pathways, suggesting that NFAT activation may be a part of the UV response. The nuclear factor of activated T cells (NFAT)1 was originally described as a transcriptional factor expressed in activated T cells but not resting T cells (1-4). The induction of NFAT in T cells required a calcium-activated signaling pathway and was blocked by cyclosporin A (CsA) and FK506 (5-11). Over the last decade, studies from several laboratories have indicated that the preexisting/cytoplasmic component of NFAT was a mixture of proteins belonging to a novel family of transcription factors (12)(13)(14). The first member of the family (NFATp, later renamed NFAT 1 ) was purified from cytoplasmic extracts of a murine T cell cloned by affinity chromatography using the distal NFAT site of murine IL-2 promoter (9, 15) and cloned from murine (Ar-5) and human (Jurkat) T cell cDNA libraries (15,16). Other distinct proteins belonging to the same family, such as NFATc, NFAT 3 , and NFAT 4 , were isolated and cloned (17-20). There are three functional domains in NFAT family proteins: the Rel similarity domain, which is responsible for the DNA binding activity and interaction with AP-1; the NFAT homology region, which regulates the intracellular localization; and the transcriptional activation domain (21). The activation of NFAT in T cells includes dephosphorylation, nuclear translocation, and increase in affinity for DNA binding (5). Stimuli that elicit calcium mobilization result in rapid dephosphorylation of NFAT proteins and their translocation to the nucleus; the dephosphorylated proteins show increased affinity for DNA binding (5).Growing evidence indicates that NFAT is not only a T cellspecific transcriptional factor but is also expressed in a variety of lympho...

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Involvement of Nuclear Factor of Activated T Cells Activation in UV Response

Huang

Mattjus

et al. 2000

Journal of Biological Chemistry

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“…Calcineurin has been shown to promote the expression of CCL2 in vascular myocytes and to mediate vascular inflammation (48). The immunosuppressive drug cyclosporin A inhibits cytokine gene expression by blocking calcineurin-mediated NFAT activation (46,49). To determine the role of carboxyl terminus of PAFR and receptor phosphorylation on PAF-induced calcineurin activation, we coexpressed PAFR, mPAFR, or ⌬ST-PAFR with NFAT and NF-B luciferase constructs.…”

Section: Resultsmentioning

confidence: 99%

Platelet-activating Factor-induced Chemokine Gene Expression Requires NF-κB Activation and Ca2+/Calcineurin Signaling Pathways

Venkatesha

Ahamed

Nuesch

et al. 2004

Journal of Biological Chemistry

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“…It has been reported that NFAT 1 and NFAT 2 mRNAs have been detected in brain, heart, skeletal muscle, testis, placenta, pancreas, small intestine, prostate, colon, skin tumors, as well as in lung (15,32). NFAT expression or NFAT-derived transactivation has also been described in several types of nonlymphoid cells, including mast (43), endothetial (44), neuronal (45), vascular smooth muscle (46), and liver-derived Chang cells (47). In this study, we have found that exposure of either mouse embryo fibroblasts (PW cells) or mouse epidermal cells (Cl 41) resulted in marked activation of NFAT-dependent transcription.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been reported that phosphorylation of NFAT is regulated by several protein kinases, including GSK 3 and JNK 2 (15, 49 -51). Other than lymphocytes, NFAT activation has been demonstrated in only a few cell types, such as vascular smooth muscle cells following induction with platelet-derived growth factor and liver-derived Chang cells following exposure to hepatitis B virus ϫ protein (46,47). The results obtained from the present investigation show that vanadium alone could induce an increase of NFAT activity of more than 10-fold.…”

Section: Fig 7 Synergistic Effect Of A23187 and Ionomycin On Vanadimentioning

confidence: 99%

Vanadium-induced Nuclear Factor of Activated T Cells Activation through Hydrogen Peroxide

Huang

Ding

et al. 2001

Journal of Biological Chemistry

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Vanadium is a transition metal widely distributed in the environment. Occupational exposure to vanadium is common in oil-fired electrical generating plants and the petrochemical, steel, and mining industries (1). The available data from the literature provides evidence that in mammalian cell culture systems vanadium(V) is biologically more active than vanadium(IV) in inducing toxic effects (2). It has been reported that the cell can protect itself against vanadate toxicity by reduced glutathione-mediated conversion of vanadium(V) to vanadium(IV), whereas vanadate(IV) does not undergo any change in valency state in BALB/3T3 cells (2). It has been found that vanadium-containing compounds exert potent toxic and carcinogenic effects, such as DNA damage and cell transformation (3-5). In animal studies, vanadium compounds or vanadiumcontaining air pollution particles have been shown to induce inflammation in the respiratory tract (6, 7). It has been reported that vanadium associated with air pollution particles, such as residual oil fly ash, can induce the synthesis and expression of inflammatory cytokines, such as IL-6, 1 IL-8, and TNF-␣ (6 -9). Vanadium exposure in vitro was also found to cause the production of IL-1, TNF-␣, and prostaglandin E2 (6, 10).The nuclear factor of activated T cells (NFAT) was originally described as a transcriptional factor expressed in activated but not resting T cells (11)(12)(13)(14). The induction of NFAT in T cells required a calcium-activated signaling pathway and was blocked by cyclosporin A (CsA) and FK506 (15-21). Over the last decade, studies from several laboratories have indicated that the pre-existing/cytoplasmic component of NFAT was a mixture of proteins belonging to a novel family of transcription factors (22)(23)(24). The first member of this family (NFATp, later renamed NFAT 1 ) was purified from cytoplasmic extracts of a murine T cell cloned by affinity chromatography using the distal NFAT site of murine 25) and cloned from murine (Ar-5) and human (Jurkat) T cell cDNA libraries (25,26). Other distinct proteins belonging to the same family, such as NFATc, NFAT 3 , and NFAT 4 , were also isolated and cloned (27-30). There are three functional domains in NFAT family proteins: the Rel-similarity domain, which is responsible for DNA-binding activity and interaction with AP-1; the NFAT-homology region, which regulates intracellular localization; and the transcriptional activation domain (31). The activation of NFAT in T cells includes dephosphorylation, nuclear translocation, and an increase in affinity for DNA binding (15). Stimuli that elicit calcium mobilization result in rapid dephosphorylation of NFAT proteins and their translocation to the nucleus. These dephosphorylated proteins show increased affinity for DNA binding (15).

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The Cyclosporin A-sensitive Nuclear Factor of Activated T Cells (NFAT) Proteins Are Expressed in Vascular Smooth Muscle Cells

Cited by 94 publications

References 42 publications

Involvement of Nuclear Factor of Activated T Cells Activation in UV Response

Involvement of Nuclear Factor of Activated T Cells Activation in UV Response

Platelet-activating Factor-induced Chemokine Gene Expression Requires NF-κB Activation and Ca2+/Calcineurin Signaling Pathways

Vanadium-induced Nuclear Factor of Activated T Cells Activation through Hydrogen Peroxide

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