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Discovery of a bis‐phosphokinetic motif in a regulatory region of the transcription factor, BCL11B
Author(s) -
Filtz Theresa Marie,
Vogel Walter K.,
Gafken Philip R.,
Leid Mark
Publication year - 2013
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/fasebj.27.1_supplement.1038.2
Subject(s) - sumo protein , phosphorylation , dephosphorylation , transcription factor , serine , chemistry , microbiology and biotechnology , threonine , kinase , biology , phosphatase , biochemistry , ubiquitin , gene
BCL11B is a haploinsufficient tumor suppressor and transcription factor that is absolutely required for thymocyte development. Stimulation of thymocytes through the MAP kinase pathways alters the phosphorylation and sumoylation of BCL11B on 19 of 23 previously identified phosphorylated residues and 2 sumoylated residues. Composite modifications of BCL11B post‐stimulation include hyperphosphorylation at 5 min, dephosphorylation at 30 min and subsequent increased sumoylation at 60 min. We sought to define the kinetics of individual sites of BCL11B phosphorylation and sumoylation to better understand the role of these modifications in integrating extracellular signals to nuclear function in developing thymocytes. Using quantitative mass spectrometry to analyze BCL11B from natively‐expressing thymocytes, we identified four distinct phosphokinetic patterns among the 19 sites and the sumoylation kinetics of one site. Further, we have identified two peptides of bis‐phosphorylated residues with the motif TPPXXSP in which stimulation‐dependent dephosphorylation of threonine is accompanied by a bimodal regulation of serine. The bis‐phosphorylated peptides are within a previously identified protein‐protein interaction and putative sumoylation‐regulatory domain of BCL11B. (This work was supported by the NIH, grant R15 GM096243, and the OSU College of Pharmacy.)