TRAF3 regulation of inhibitory signaling pathways in B and T lymphocytes by kinase and phosphatase localization

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Alicia M. Wallis¹  Gail A. Bishop¹ 

[1] Graduate Program in Immunology;Department of Microbiology & Immunology, The University of Iowa;Department of Internal Medicine, The University of Iowa;Veterans’ Affairs Medical Center

关键词: B cell;    signal transduction;    T cell;    TRAF;   

DOI  :  10.1002/JLB.2MIR0817-339RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling. An important biological consequence of this inhibition is restraining the size of the plasma cell compartment, as their differentiation is IL-6 dependent. Similarly, in T lymphocytes, interleukin 2 receptor (IL2R) signaling recruits TRAF3, which in turn recruits the phosphatase TCPTP (T cell protein tyrosine phosphatase) to dephosphorylate JAK3. The resulting inhibition of IL-2R signaling limits the IL-2-dependent size of the T regulatory cell (Treg) compartment. TRAF3 also inhibits type 1 IFN receptor (IFN?R) signaling to T cells by this mechanism, restraining expression of IFN-stimulated gene expression. In contrast, TRAF3 association with two inhibitors of TCR signaling, C-terminal Src kinase (Csk) and PTPN22, promotes their localization to the cytoplasm, away from the membrane TCR complex. TRAF3 thus enhances TCR signaling and downstream T cell activation. Implications are discussed for these regulatory roles of TRAF3 in lymphocytes, as well as potential future directions.

【 授权许可】

CC BY