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c‐Abl mediates high NaCl‐induced phosphorylation and activation of the transcription factor TonEBP/OREBP
Author(s) -
Gallazzini Morgan,
Yu MingJiun,
Gunaratne Ruwan,
Burg Maurice B.,
Ferraris Joan D.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-157362
Subject(s) - phosphorylation , microbiology and biotechnology , chemistry , abl , tyrosine kinase , transcription factor , kinase , tyrosine phosphorylation , cancer research , biology , signal transduction , biochemistry , gene
The transcription factor TonEBP/OREBP promotes cell survival during osmotic stress. High NaCl‐induced phosphorylation of TonEBP/OREBP at tyrosine‐143 was known to be an important factor in increasing its activity in cell culture. We now find that TonEBP/OREBP also is phosphorylated at tyrosine‐143 in rat renal inner medulla, dependent on the interstitial osmolality. c‐Abl seemed likely to be the kinase that phosphorylates TonEBP/OREBP because Y143 is in a consensus c‐Abl phosphorylation site. We now confirm that, as follows. High NaCl increases c‐Abl activity. Specific inhibition of c‐Abl by imatinib, siRNA, or c‐Abl kinase dead drastically reduces high NaCl‐induced TonEBP/OREBP activity by reducing its nuclear location and transactivating activity. c‐Abl associates with TonEBP/OREBP (coimmunoprecipitation) and phosphorylates TonEBP/OREBP‐Y143 both in cell and in vitro . High NaCl‐induced activation of ataxia telangiectasia mutated, previously known to contribute to activation of TonEBP/OREBP, depends on c‐Abl activity. Thus, c‐Abl is the kinase responsible for high NaCl‐induced phosphorylation of TonEBP/OREBP‐Y143, which contributes to its increased activity.—Gallazzini, M., Yu, M.‐J., Gunaratne, R., Burg, M. B., Ferraris, J. D. c‐Abl mediates high NaCl‐induced phosphorylation and activation of the transcription factor TonEBP/OREBP. FASEB J . 24, 4325–4335 (2010). www.fasebj.org