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A novel splicing variant form suppresses the activity of full‐length signal transducer and activator of transcription 5A
Author(s) -
Watanabe Yoshihisa,
Ikegawa Masaya,
Naruse Yoshihisa,
Tanaka Masaki
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07339.x
Subject(s) - stat5 , microbiology and biotechnology , biology , transactivation , rna splicing , exon , transcription factor , nuclear localization sequence , phosphorylation , transcription (linguistics) , nucleus , genetics , gene , rna , linguistics , philosophy
Signal transducers and activators of transcription (STATs) regulate a variety of cellular functions, including differentiation and proliferation. STAT3 and STAT5 are known to play important roles in brain processes, such as energy homeostasis and neuronal development. We isolated a novel splicing variant of STAT5A from a cDNA library of the mouse brainstem. This variant, STAT5A_ΔE18 , lacked exon 18 and caused a frameshift in the C‐terminus, resulting in deletion of a tyrosine phosphorylation site and a transactivation domain. Although the frameshift region had no characteristic motifs, it was highly serine/threonine‐rich and contained a short proline‐rich sequence. Expression of STAT5A_ΔE18 was detected in the mouse brainstem, lung and thymus, but not in the mouse cerebrum or cerebellum. We developed a specific antibody against STAT5A_ΔE18 and investigated the intracellular localization of this variant. STAT5A_ΔE18 showed dot‐like structures in the cytoplasm and could not translocate into the nucleus after prolactin treatment. STAT5A_ΔE18 showed a strong tendency to aggregate, which led to coaggregation with STAT5A_full‐length. This coaggregation inhibited the nuclear transport of STAT5A and suppressed prolactin‐induced activation of STAT5A.