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The role of PKC η in T cell development and activation
Author(s) -
Fu Guo,
Niederberger Nathalie,
Gascoigne Nicholas RJ
Publication year - 2008
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.22.1_supplement.661.12
Subject(s) - protein kinase c , microbiology and biotechnology , immunological synapse , thymocyte , t cell , cd8 , cd3 , t cell receptor , biology , kinase , signal transduction , knockout mouse , chemistry , antigen , immunology , receptor , biochemistry , immune system
Protein kinase C (PKC) is a family of serine‐ and threonine‐specific protein kinases. PKC family members phosphorylate a wide variety of proteins and are involved in diverse cellular signaling pathways. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. Among the PKC isoforms expressed in T cells (e.g.α, β, δ, η,ζ), only PKC θ has been shown to be recruited to the immunological synapse. PKC θ knockout mice showed a profound peripheral T cell defects due to loss of TCR‐initiated NFκB activation, but normal T cell development. These data suggest a redundant role of PKC θ in T cell development, and hence there are possibly other PKC isoforms replacing the role of PKCθ. We found that PKC η is upregulated after TCR ligation in developing thymocytes, and is expressed at an earlier stage of thymocyte development in the absence of PKCθ. Also, like PKCθ, PKC η is rapidly recruited to the immunological synapse during antigen‐recognition, unlike other PKCs. To examine the effect of PKC ηon thymocyte development, we transduced PKC θ −/&minus bone marrow cells with retroviruses expressing PKC η specific shRNA cassette and performed bone marrow reconstitution assay. Preliminary data showed that knock‐down of PKC η, in the absence of PKC θ, led to a decrease of SP cells (both CD4 + and CD8 + ), and an increase DP cells (CD4 + CD8 + ). Taken together, these results suggest that PKC η may play an important non‐redundant role in T cell development and activation. In order to more thoroughly investigate the biological functions of PKC η, we had made a PKC η conditional knock‐out mice and are currently working on them. This study is supported by NIH grant 5R01GM048002‐14.