Calcium dependent activation of the NF‐AT transcription factor by p59fyn

Baldari, Cosima T.; Heguy, Adriana; Telford, John L.

doi:10.1016/0014-5793(93)81346-2

Cited by 23 publications

(35 citation statements)

References 20 publications

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“…Conversely, we and other have previously shown that an oncogenic, constitutively active Ras mutant strongly synergized with an increase in intracellular free calcium and reconstituted full NF-AT activation (Baldari et al, 1993;Woodrow et al, 1993a). One possibility is that, while the Ras mutant used in these studies lacked GTPase activity and was thus permanently in the active state, localization of Shc to the membrane triggers the physiological pathway of Ras activation, implying repeated cycles of upregulation and downregulation of Ras activity and a net Ras activity under a critical threshold.…”

Section: Discussionmentioning

confidence: 63%

“…As shown in Figure 6, luciferase activity was increased by 200% in cells expressing HAShc-MLS as compared to parental cells, while HA-Shc had no signi®cant e ect. Since a constitutively active mutant of Ras can synergize with a calcium ionophore in inducing NF-AT activation (Baldari et al, 1993;Woodrow et al, 1993a), cells were also activated with the calcium ionophore A23187. No signi®cant luciferase activity was observed in the absence of stimulation or in the presence of A23187 in any of the lines (data not shown).…”

Section: Enhancement Of Tcr Dependent Activation Of the Transcriptionmentioning

confidence: 99%

“…Transfections, luciferase and CAT assays, and flow cytometry Transfections were carried out as described using a modi®ca-tion of the DEAE-dextran procedure (Baldari et al, 1993). To minimize variability among samples, activations were carried out on aliquots of a single pool of transfected cells.…”

Section: Plasmids and Antibodiesmentioning

confidence: 99%

“…Cells were collected 8 ± 10 h after activation and assayed for luciferase activity using the protocol from Promega (Madison, WI, USA). CAT assays were carried out as described (Baldari et al, 1993) using equal amounts of proteins for each sample. Thin layer chromatograms were scanned and chloramphenicol acetylation was quantitated using a Phosphorimager (Molecular Dynamics, Sunnyvale, CA, USA).…”

Section: Plasmids and Antibodiesmentioning

confidence: 99%

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Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane rafts

et al. 2000

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Section: Discussionmentioning

confidence: 63%

Section: Enhancement Of Tcr Dependent Activation Of the Transcriptionmentioning

confidence: 99%

Section: Plasmids and Antibodiesmentioning

confidence: 99%

Section: Plasmids and Antibodiesmentioning

confidence: 99%

See 2 more Smart Citations

Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane rafts

et al. 2000

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“…In the nucleus NFAT assembles in cooperative DNAbinding complexes with dimers of the AP-1 family of transcription factors (4,9). Complementation studies using constitutively active mutants of signaling proteins have shown that the calcium/calcineurin and the Ras/protein kinase C/mitogen-activated protein kinase pathways are integrated at the level of NFAT proteins (10,11). The NFAT family of transcription factors includes to date five members, NFAT1 (also named NFATp or NFATc2), NFAT2 (also named NFATc or NFATc1), NFAT3 (also named NFATc4), NFAT4 (also named NFATc3), and the recently identified atypical member NFAT5 (12)(13)(14)(15)(16)(17)(18).…”

Section: Initially Described As a Transcriptional Complex That Bound mentioning

confidence: 99%

Identification and Characterization of a Novel Nuclear Factor of Activated T-cells-1 Isoform Expressed in Mouse Brain

Plyte

Boncristiano

Fattori

et al. 2001

Journal of Biological Chemistry

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The nuclear factor of activated T-cells (NFAT) family transcription factors play a key role in the control of cytokine gene expression in T-cells. Although initially identified in T-cells, recent data have unveiled unanticipated roles for NFATs in the development, proliferation, and differentiation of other tissues. Here we report the identification, cDNA cloning, and functional characterization of a new isoform of NFAT1 highly expressed in mouse brain. This isoform, which we named NFAT1-D, is identical to NFAT1 throughout the N-terminal regulatory domain and the portion of the Rel domain which includes the minimal region required for specific binding to DNA and interaction with AP-1. The homology stops sharply upstream of the 3-boundary of the Rel homology domain and is followed by a short unique C-terminal region. NFAT1-D was expressed at high levels in all brain districts and was found as a constitutively active transcription complex. Transfection of a NFAT/luciferase reporter in the neuronal cell line PC12, which also expresses NFAT1-D, showed that these cells expressed a constitutive NFAT activity that was enhanced after nerve growth factor-induced differentiation but was resistant to the immunosuppressant cyclosporin A. NFAT1-D was, however, inducibly activated in a cyclosporin A-sensitive manner when expressed in Tcells, suggesting that the activity of NFAT proteins might be controlled by their specific cellular context. Initially described as a transcriptional complex that bound a T-cell antigen receptor (TCR)1 response element on the interleukin (IL)-2 gene enhancer, nuclear factor of activated T-cells (NFAT) is a family of transcription factors crucially involved in the regulation of cytokine gene expression in T-cells (1). NFAT activity is strongly unregulated after TCR triggering; however, receptor engagement can be bypassed by a combination of phorbol esters and calcium ionophores, which activate protein kinase C and induce a rise in intracellular calcium ions, respectively. This dual requirement reflects the subunit composition of NFAT factors, which includes a cytoplasmic and a nuclear component. In resting cells, NFAT is found as a cytosolic protein phosphorylated on serine residues. After an elevation in intracellular calcium ions, the calmodulin-dependent phosphatase calcineurin is activated and dephosphorylates NFAT, exposing a nuclear localization sequence near the N terminus of NFAT and resulting in its translocation to the nucleus (2-5). This process is exquisitely sensitive to the immunosuppressants cylosporin A (CsA) and FK506, which interact with specific cytosolic receptors and form complexes that bind with high affinity to calcineurin and lock it in an inactive conformation (6 -8). In the nucleus NFAT assembles in cooperative DNAbinding complexes with dimers of the AP-1 family of transcription factors (4, 9). Complementation studies using constitutively active mutants of signaling proteins have shown that the calcium/calcineurin and the Ras/protein kinase C/mitogen-activated protein ki...

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Dissection of T cell antigen receptor signaling using protein tyrosine kinase inhibitors

Baldari

Telford

1994

Eur J Immunol

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T cell antigen receptor (TcR) recognition of appropriately presented antigen results in the rapid activation of protein tyrosine kinases. Subsequent events include activation of protein kinase C and increased intracellular free calcium which lead to the activation of transcription factors involved in regulating interleukin-2 gene expression. We have assayed the ability of a panel of protein tyrosine kinase (PTK) inhibitors to interfere with activation of the NF-AT transcription factor by TcR ligation or treatment with phorbol ester and calcium ionophore which bypass many of the early events of TcR signal transduction. The results indicate that PTK are involved in early and late stages of TcR signaling. Moreover, one inhibitor (genistein) revealed the existence of a PTK which down-regulates specifically calcium-mediated signaling at a point downstream of the PTK p56lck but upstream of calcium mobilization.

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Calcium dependent activation of the NF‐AT transcription factor by p59fyn

Cited by 23 publications

References 20 publications

Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane rafts

Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane rafts

Identification and Characterization of a Novel Nuclear Factor of Activated T-cells-1 Isoform Expressed in Mouse Brain

Dissection of T cell antigen receptor signaling using protein tyrosine kinase inhibitors

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