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Association of UDP‐Glucuronosyltransferases with 14‐3‐3 Chaperone Protein and Kinase‐dependent Signaling Partners
Author(s) -
Basu Nikhil K,
Basu Mousumi,
Mitra Partha S,
Banerjee Rajat,
Owens Ida S
Publication year - 2009
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.23.1_supplement.709.6
Subject(s) - phosphorylation , calphostin c , protein kinase c , chemistry , serine , dephosphorylation , biochemistry , signal transduction , immunoprecipitation , microbiology and biotechnology , kinase , chaperone (clinical) , biology , phosphatase , gene , medicine , pathology
UDP‐glucuronosyltransferase (UGT) isozymes eliminates from the body a vast number of lipophilic metabolites, therapeutic drugs and chemical toxins that include dietary constituents and environmental contaminants by increasing water solubility via conversion to glucuronides. Recently, we uncovered the fact that UGT isozymes require phosphorylation for activity. Phosphorylation, regulated via signaling, occurs on serine/threonine and tyrosine residues. Inasmuch as UGT1A7His and PKCε co‐localized in 1A7‐transfected COS‐1 cells, we attempted to co‐immunoprecipitate the two proteins with anti‐His from solubilized cellular extracts and analyze for related proteins. Curcumin (75 µM) caused complete disassociation of β‐COP and PKCε and dephosphorylation of UGT1A7, whereas 500 nM calphostin‐C completely disassociated PKCε and β‐COP. The coordinate loss of PKCε and β‐COP with dephosphorylation of UGT following curcumin or calphostin‐C treatment indicates these factors are likely located in a complex that supports UGT1A7 activity. Similarly, both PKCα and PKCδ, but not PKCε, co‐localized and co‐immunoprecipitated with UGT1A10‐His. Further, finding 1A7 in a 225‐kDa complex with phospho‐serine 14‐3‐3 chaperone protein during purification demonstrated UGT is associated within a signaling unit consistent with regulated phosphorylation, predictably maintaining stability of UGT proteins. ε