Nuclear factor of activated T cells 2 transactivation in mast cells: a novel isoform-specific transactivation domain confers unique FcepsilonRI responsiveness.
J Biol Chem
; 278(29): 26695-703, 2003 Jul 18.
Article
in En
| MEDLINE
| ID: mdl-12738787
ABSTRACT
Murine nuclear factor of activated T cells (NFAT)2.alpha/beta differ by 42 and 28 unique amino-terminal amino acids and are differentially expressed. Both isoforms share conserved domains that regulate DNA-binding and subcellular localization. A genetic "one-hybrid" assay was used to define two distinct transactivation (TA) domains in addition to a conserved TAD present in both isoforms, a second, novel TAD exists within the beta-specific amino terminus. Pharmacologic inhibitors Gö6976 and rottlerin demonstrate that both conventional and novel protein kinase C (PKC) family members regulate endogenous mast cell NFAT activity, and NFAT2 TA. Overexpression of dominant active PKC (which has been implicated in immune receptor signaling) induces NFAT2.alpha/beta TA. Mutations within the smallest PKC-responsive transactivation domain demonstrate that the PKC effect is at least partially indirect. Significantly, the beta-specific domain confers greater ability to TA in response to treatment with phorbol 12-myristate 13-acetate/ionomycin or lipopolysaccharide, and unique sensitivity to FcepsilonRI signaling. Accordingly, overexpression of NFAT2.beta results in significantly greater NFAT- and interleukin-4 reporter activity than NFAT2.alpha. These results suggest that whereas NFAT2 isoforms may share redundant DNA-binding preferences, there are specialized functional consequences of their isoform-specific domains.
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Database:
MEDLINE
Main subject:
Transcription Factors
/
Nuclear Proteins
/
Receptors, IgE
/
DNA-Binding Proteins
/
Mast Cells
Language:
En
Journal:
J Biol Chem
Year:
2003
Type:
Article
Affiliation country:
United States