Ca(2+)-dependent gene expression mediated by MEF2 transcription factors.
Ca(2+) induction of a subset of cellular and viral immediate-early activation genes in lymphocytes has been previously mapped to response elements recognized by the MEF2 family of transcription factors. Here, we demonstrate that Ca(2+) activation of MEF2 response elements in T lymphocytes is mediated in synergy by two Ca(2+)/calmodulin-dependent enzymes, the phosphatase calcineurin, and the kinase type IV/Gr (CaMKIV/Gr), which promote transcription by the MEF2 family members MEF2A and MEF2D. Calcineurin up-regulates the activity of both factors by an NFAT-dependent mechanism, while CaMKIV/Gr selectively and independently activates MEF2D. These results identify MEF2 proteins as effectors of a pathway of gene induction in T lymphocytes which integrates diverse Ca(2+) activation signals and may be broadly operative in several tissues.
Blaeser
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F
Department of Pediatrics, Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ho
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Prywes
R
R
Chatila
T A
TA
D000818:Animals; D001483:Base Sequence; D019703:Calcineurin / Q000378:metabolism; D020013:Calcium Signaling; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011994:Recombinant Proteins / Q000378:metabolism; D020218:Response Elements; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; C578043:MEF2D protein, human; C578036:Mef2a protein, mouse; C578044:Mef2d protein, mouse; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; C539821:NR4A1 protein, human; C539818:Nr4a1 protein, mouse; D009687:Nuclear Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D014157:Transcription Factors; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517685:Camk4 protein, mouse; D019703:Calcineurin