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Phospho‐STAT5 accumulation in nuclear fractions from vitamin A‐deficient rat liver
Author(s) -
Murray Michael,
Butler Alison M.,
Fiala-Beer Eva,
Su Gloria M.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.052
Subject(s) - endocrinology , medicine , stat5 , phosphorylation , protein tyrosine phosphatase , biology , tyrosine , janus kinase 2 , janus kinase , dephosphorylation , chemistry , phosphatase , biochemistry
The growth hormone (GH)‐responsive cytochrome P450 (CYP) 2C11 is down‐regulated in vitamin A‐deficient (VAD) rat liver. This study assessed the impact of a VAD diet on the hepatic Janus kinase‐Signal Transducers and Activators of Transcription (JAK‐STAT) system that mediates GH signalling. Nuclear tyrosine‐ and serine‐phosphorylated STAT5 accumulated in VAD liver, whereas nuclear JAK2 tyrosine kinase and SHP‐1 phosphatase were decreased. Tyrosine‐phosphorylated SHP‐1 was decreased to 36 ± 14% of control ( P < 0.01), indicating its impaired activation in VAD liver. Episodic GH pulses increased nuclear phospho‐STAT5, especially in control liver, but nuclear phospho‐JAK2 and phospho‐SHP‐1 were not restored. CYP2C11 protein and testosterone 16α‐hydroxylation were decreased in VAD liver to 67 ± 16% and 76 ± 19% of control, and were further decreased by GH to 32 ± 8% and 30 ± 14% of control. Thus, hypo‐responsiveness of JAK‐STAT in VAD liver is associated with impaired nuclear phospho‐STAT dephosphorylation.