STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription

The 89-kDa STAT3 protein is a latent transcription factor which is activated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific receptor activates JAK2 which leads to the tyrosine phosphorylation of STAT3 proteins. Here...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-05, Vol.271 (22), p.13221-13227
Main Authors: Caldenhoven, E, van Dijk, T B, Solari, R, Armstrong, J, Raaijmakers, J A, Lammers, J W, Koenderman, L, de Groot, R P
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cloning, Molecular
DNA, Complementary
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Humans
Molecular Sequence Data
Phosphorylation
Repressor Proteins - genetics
Repressor Proteins - metabolism
RNA Splicing
Sequence Homology, Nucleic Acid
STAT3 Transcription Factor
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription, Genetic - genetics
Tyrosine - metabolism
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Summary:The 89-kDa STAT3 protein is a latent transcription factor which is activated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific receptor activates JAK2 which leads to the tyrosine phosphorylation of STAT3 proteins. Here we report the cloning of a cDNA encoding a variant of the transcription factor STAT3 (named STAT3beta) which was isolated by screening an eosinophil cDNA library. Compared to wild-type STAT3, STAT3beta lacks an internal domain of 50 base pairs located near the C terminus. This splice product is a naturally occurring isoform of STAT3 and encodes a 80-kDa protein. We found by reconstitution of the human IL-5R in COS cells that like STAT3, STAT3beta is phosphorylated on tyrosine and binds to the pIRE from the ICAM-1 promoter after IL-5 stimulation. However, STAT3beta fails to activate a pIRE containing promoter in transient transfection assays. Instead, co-expression of STAT3beta inhibits the transactivation potential of STAT3. These results suggests that STAT3beta functions as a negative regulator of transcription.
ISSN:0021-9258