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PMID: 8691123 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Activation protein 1-dependent transcriptional activation of interleukin 2 gene by Ca2+/calmodulin kinase type IV/Gr.

The Journal of experimental medicine ·Vol. 184 ·No. 1 ·1996-07-01 ·Pages 101-12

Ho N, Gullberg M, Chatila T

Abstract

The Ca2+/calmodulin-dependent protein kinase (CaMK) type IV/Gr is selectively expressed in T lymphocytes and is activated after signaling via the T cell antigen receptor (TCR), indicating that it mediates some of the Ca(2+)-dependent transcriptional events that follow TCR engagement. Here we show that CaMKIV/Gr induces the transcription factor activation protein 1 (AP-1) alone or in synergy with T cell mitogens and with the p21ras oncoprotein. CaMKIV/ Gr signaling is associated with transcriptional activation of c-fos but is independent of p21ras or calcineurin. AP-1 is an integral component of the nuclear factor of activated T cells (NFAT) transcriptional complex, which is required for interleukin 2 gene expression in T cells. We demonstrate that CaMKIV/Gr reconstitutes the capacity of the cytosolic component of NFAT to direct transcription from NFAT sites in non-T cells. These results reveal a central role for CaMKIV/Gr as a Ca(2+)-regulated activator of gene transcription in T lymphocytes.

MeSH Terms
Base Sequence Calcium/physiology Calcium-Calmodulin-Dependent Protein Kinase Type 4 Calcium-Calmodulin-Dependent Protein Kinases/physiology Cell Nucleus/metabolism DNA-Binding Proteins/metabolism Enhancer Elements, Genetic Gene Expression Regulation Humans Interleukin-2/genetics Molecular Sequence Data NFATC Transcription Factors Nuclear Proteins Oligodeoxyribonucleotides/chemistry Promoter Regions, Genetic T-Lymphocytes/physiology Transcription Factor AP-1/physiology Transcription Factors/metabolism Transcription, Genetic Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins Interleukin-2 NFATC Transcription Factors Nuclear Proteins Oligodeoxyribonucleotides Transcription Factor AP-1 Transcription Factors CAMK4 protein, human Calcium-Calmodulin-Dependent Protein Kinase Type 4 Calcium-Calmodulin-Dependent Protein Kinases Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ho N
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Gullberg M
Chatila T
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47 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.1.101
Published
1996-07-01
Pages
101-12
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192676
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.184.1.101 PMC Full Text View journal details
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