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Monocyte 15‐lipoxygenase expression is regulated by a novel cytosolic signaling complex with PKC delta and tyrosine phosphorylated Stat3
Author(s) -
Bhattacharjee Ashish,
Xu Bo,
Frank David,
Feldman Gerald,
Cathcart Martha
Publication year - 2006
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.20.4.a635-a
Subject(s) - tyrosine phosphorylation , phosphorylation , microbiology and biotechnology , cytosol , arachidonate 5 lipoxygenase , chemistry , signal transduction , tyrosine , monocyte , protein kinase c , tyrosine kinase , biochemistry , biology , enzyme , arachidonic acid , immunology
Our previous studies demonstrated that IL‐13‐induced 15‐lipoxygenase (15‐LO) expression in human monocytes is regulated by the activation of both Stat1 and Stat3 and by PKCδ. IL‐13 stimulated the phosphorylation of Stat3 on both Tyr705 and Ser727. In this study we show that IL‐13 induces the association of PKCδ with Stat3, not with Stat1, and is required for Stat3S727 phosphorylation. We found that the IL‐13‐dependent, novel signaling complex of PKCδ and Stat3 occurs almost exclusively in the cytosol and that the Stat3 in the complex is tyrosine phosphorylated. From our preliminary results we hypothesized that tyrosine phosphorylation was required for Stat3 interaction with PKCδ and subsequent PKCδ‐dependent phosphorylation of Stat3S727. Using an efficient transfection protocol for human monocytes, we showed that expression of Stat3 containing a mutation in Y705 inhibited the association of PKCδ with Stat3 and blocked Stat3S727 phosphorylation whereas transfection with wild‐type Stat3 did not. Our results indicate that Stat3Y705 phosphorylation is a prerequisite for the IL‐13–stimulated association of Stat3 with cytosolic PKCδ and the Stat3S727 phosphorylation. Furthermore, by transfecting monocytes with Stat3 containing mutations in Y705 and S727 or with wild type Stat3, we demonstrated that both Stat3 tyrosine and serine phosphorylations are required for optimal binding of Stat3 with DNA as well as for maximal expression of 15‐LO, an important regulator of inflammation and apoptosis. (This work was funded by HL51068)