Key points are not available for this paper at this time.
CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and is expressed on T, B, and NK cells. The signal via CD27 plays pivotal roles in T-T and T-B cell interactions. Here we demonstrate that overexpression of CD27 activates NF-κB and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that the C-terminal PIQEDYR motif was indispensable for both NF-κB and SAPK/JNK activation and was also required for the interaction with TNF receptor-associated factor (TRAF) 2 and TRAF5, both of which have been implicated in NF-κB activation by members of the TNF-R superfamily. Co-transfection of a dominant negative TRAF2 or TRAF5 blocked NF-κB and SAPK/JNK activation induced by CD27. Recently, a TRAF2-interacting kinase has been identified, termed NF-κB-inducing kinase (NIK). A kinase-inactive mutant NIK blocked CD27-, TRAF2-, and TRAF5-mediated NF-κB and SAPK/JNK activation. These results indicate that TRAF2 and TRAF5 are involved in NF-κB and SAPK/JNK activation by CD27, and NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-κB and SAPK/JNK activation. CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and is expressed on T, B, and NK cells. The signal via CD27 plays pivotal roles in T-T and T-B cell interactions. Here we demonstrate that overexpression of CD27 activates NF-κB and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that the C-terminal PIQEDYR motif was indispensable for both NF-κB and SAPK/JNK activation and was also required for the interaction with TNF receptor-associated factor (TRAF) 2 and TRAF5, both of which have been implicated in NF-κB activation by members of the TNF-R superfamily. Co-transfection of a dominant negative TRAF2 or TRAF5 blocked NF-κB and SAPK/JNK activation induced by CD27. Recently, a TRAF2-interacting kinase has been identified, termed NF-κB-inducing kinase (NIK). A kinase-inactive mutant NIK blocked CD27-, TRAF2-, and TRAF5-mediated NF-κB and SAPK/JNK activation. These results indicate that TRAF2 and TRAF5 are involved in NF-κB and SAPK/JNK activation by CD27, and NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-κB and SAPK/JNK activation. CD27 is a member of the tumor necrosis factor receptor (TNF-R) 1The abbreviations used are: TNF, tumor necrosis factor; TNF-R, TNF receptor; TRAF, TNF receptor-associated factor; LT-βR, lymphotoxin-β receptor; HEK, human embryonic kidney; HVEM, herpesvirus entry mediator; SAPK, stress-activated protein kinase; JNK, c-Jun N-terminal kinase; NIK, NF-κB-inducing kinase; EMSA, electrophoretic mobility shift assay; mAb, monoclonal antibody; HA, hemagglutinin; PCR, polymerase chain reaction.1The abbreviations used are: TNF, tumor necrosis factor; TNF-R, TNF receptor; TRAF, TNF receptor-associated factor; LT-βR, lymphotoxin-β receptor; HEK, human embryonic kidney; HVEM, herpesvirus entry mediator; SAPK, stress-activated protein kinase; JNK, c-Jun N-terminal kinase; NIK, NF-κB-inducing kinase; EMSA, electrophoretic mobility shift assay; mAb, monoclonal antibody; HA, hemagglutinin; PCR, polymerase chain reaction. superfamily and is expressed on T, B, and NK cells as a disulfide-linked homodimer (1Hintzen R.Q. de Jong R. Lens S.M.A. van Lier R.A.W. Immunol. Today. 1997; 15: 307-311Abstract Full Text PDF Scopus (152) Google Scholar). CD27 ligand (CD70) belongs to the TNF superfamily and is expressed on the surface of activated T and B cells. Cross-linking of CD27 along with a suboptimal dose of phytohemagglutinin, phorbol 12-myristate 13-acetate, anti-CD2, or anti-CD3 antibodies resulted in vigorous proliferation of T cells, indicating that CD27 transmits a co-stimulatory signal in T cells (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar). On the other hand, ligation of CD27 on B cells enhanced IgG production (3Kobata T. Jacquot S. Kozlowski S. Agematsu K. Schlossman S.F. Morimoto C. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 11249-11253Crossref PubMed Scopus (152) Google Scholar). These studies implicated the important roles of CD27/CD70 interaction in immunoregulation through T-T and T-B cell interactions. A recent report also demonstrated a critical role of CD27/CD70 interaction in T cell development (4Gravestein L.A. van Ewijk W. Ossendorp F. Borst J. J. Exp. Med. 1996; 184: 675-685Crossref PubMed Scopus (40) Google Scholar). Although biological function of CD27/CD70 interaction has been extensively investigated, the mechanism by which CD27 transmits the signal has been largely unknown, except for a previous study, which demonstrated involvement of the protein tyrosine kinase cascade (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar).TNF receptor-associated factors (TRAFs) have emerged as signal transducers for some members of the TNF-R superfamily (5Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Abstract Full Text PDF PubMed Scopus (927) Google Scholar, 6Cheng G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, 7Hu H.M. O'Rourke K. Boguski M.S. Dixit V.M. J. Biol. Chem. 1995; 269: 30069-30072Abstract Full Text PDF Google Scholar, 8Regnier C.H. Tomasetto C. Moog-Lutz C. Chenard M.-P. Wendling C. Basset P. Rio M.-C. J. Biol. Chem. 1995; 270: 25715-25721Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 9Nakano H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar). All TRAFs, except for TRAF1, are composed of N-terminal zinc RING finger, multiple zinc fingers, coiled-coil, and C-terminal receptor binding (TRAF) domains (5Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Abstract Full Text PDF PubMed Scopus (927) Google Scholar, 6Cheng G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, 9Nakano H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar, 11Mosialos G. Birkenbach M. Yalamanchili R. VanArsdale T. Ware C.F. Kieff E. Cell. 1995; 80: 389-399Abstract Full Text PDF PubMed Scopus (899) Google Scholar). Whereas an N-terminal RING finger domain of TRAF2, TRAF5, and TRAF6 is responsible for NF-κB activation, the TRAF and coiled-coil domains are required for homo- and heterodimerization and receptor association (5Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Abstract Full Text PDF PubMed Scopus (927) Google Scholar, 6Cheng G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, 9Nakano H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar, 12Rothe M. Sarma Dixit V.M. Goeddel D.V. Science. 1995; 269: PubMed Scopus Google Scholar). the of other have been to with the domain and H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar, 12Rothe M. Sarma Dixit V.M. Goeddel D.V. Science. 1995; 269: PubMed Scopus Google Scholar, J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, T. S. S. T. K. S. T. G. Kieff E. T. J. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, S. H. T. R. M. K. Yagita H. Okumura K. J. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). TRAF2 has been to with domain and receptor via the H. Goeddel D.V. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, A.M. O'Rourke K. M. R. L. R. J. Dixit V.M. Science. 1996; PubMed Scopus Google Scholar, J. T. Goeddel D.V. R. Nature. 1996; PubMed Scopus Google Scholar). TRAF2, and TRAF5 also with protein the protein of G. Birkenbach M. Yalamanchili R. VanArsdale T. Ware C.F. Kieff E. Cell. 1995; 80: 389-399Abstract Full Text PDF PubMed Scopus (899) Google Scholar). TRAF2 also in the activation of stress-activated kinase (SAPK)/c-Jun N-terminal kinase induced by TNF H. Goeddel D.V. M. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, C. J. 1997; PubMed Scopus Google Scholar, G. A. A. C. M. Science. 1997; PubMed Scopus Google Scholar). and TRAF5 are involved in by G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). has been also to involved in by G. Kieff E. Ware C.F. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google Scholar). The mechanism by which NF-κB to Recently, a kinase was that with TRAF2 and activates NF-κB-inducing kinase D. Nature. 1997; PubMed Scopus Google Scholar). the role of NIK in or NF-κB activation is is to other co-stimulatory and the herpesvirus entry M.S. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). was to with TRAF2 and TRAF5 M. M. A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. R. M. W.J. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). Here we demonstrate that CD27 activates both NF-κB and which are by TRAF2 and also demonstrate that a kinase-inactive mutant of NIK TRAF2-, and NF-κB and SAPK/JNK activation. These results a role of TRAF2 and TRAF5 in CD27 and that NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-κB and SAPK/JNK have important roles of in through members of the TNF-R superfamily. we demonstrated that CD27 with TRAF2 and TRAF5, and are implicated in NF-κB and SAPK/JNK activation by CD27. results that other members of the TNF-R as and also with and NF-κB and SAPK/JNK also demonstrated that a kinase-inactive mutant NIK blocked and NF-κB activation, indicating that NIK is a common downstream kinase of TRAF2, TRAF5, and TRAF6 for NF-κB activation. studies H. Goeddel D.V. M. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, C.H. Goeddel D.V. M. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google that protein kinase responsible for and SAPK/JNK activation. Here we demonstrated that NIK also activates SAPK/JNK and a kinase-inactive mutant NIK SAPK/JNK activation by TRAF2, TRAF5, and CD27. The dominant negative of on SAPK/JNK activation by CD27 and to that on NF-κB activation. These results that other protein kinase kinase as protein kinase the dominant negative of on SAPK/JNK activation. The mechanism by which NIK activates SAPK/JNK is A previous that CD27 induced tyrosine of signal and the with a kinase blocked co-stimulatory signal through CD27 (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar). that CD27 activates is protein tyrosine and is the of which activates NF-κB and has been that CD27, LT-βR, and with both TRAF2 and TRAF5 H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, S. H. T. R. M. K. Yagita H. Okumura K. J. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar, M. M. A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. R. M. W.J. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). A common of through is the activation of NF-κB that by of a of TRAF in is involved in and proliferation in B cells J. Immunol. 1996; PubMed Google and CD27 IgG production in B cells (3Kobata T. Jacquot S. Kozlowski S. Agematsu K. Schlossman S.F. Morimoto C. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 11249-11253Crossref PubMed Scopus (152) Google Scholar). is involved in some of negative in the R. A. T. E. A. H. H. R. A. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google and is implicated in development R. van Ewijk W. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar, R. F. J. Exp. Med. 1996; 184: PubMed Scopus Google Scholar). The in in the in with the of as as for cells, which an important role in of and TRAF5 H. M. K. Ware C.F. Yagita H. Okumura K. 1997; PubMed Scopus Google or The of on receptor CD27. TRAF2 and TRAF5 have some in other the roles of TRAF2 and TRAF5 in TRAF5 with the and H. or R. J. 1997; Scopus Google Scholar). On the other hand, TRAF5 with TRAF2 These results that TRAF2 and TRAF5 through interaction with of downstream The recent of revealed that SAPK/JNK activation, NF-κB activation, by TNF is in A. D. J. F. A. de D. P. M. Goeddel D.V. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). results that a TRAF5 NF-κB activation by TNF, that TRAF2 and TRAF5 in NF-κB activation by SAPK/JNK activation by TRAF2 with a of TRAF2 to SAPK/JNK and TRAF2 to SAPK/JNK activation to TRAF2 and TRAF5 are in via CD27 and other members of the TNF-R in and CD27 is a member of the tumor necrosis factor receptor (TNF-R) 1The abbreviations used are: TNF, tumor necrosis factor; TNF-R, TNF receptor; TRAF, TNF receptor-associated factor; LT-βR, lymphotoxin-β receptor; HEK, human embryonic kidney; HVEM, herpesvirus entry mediator; SAPK, stress-activated protein kinase; JNK, c-Jun N-terminal kinase; NIK, NF-κB-inducing kinase; EMSA, electrophoretic mobility shift assay; mAb, monoclonal antibody; HA, hemagglutinin; PCR, polymerase chain reaction.1The abbreviations used are: TNF, tumor necrosis factor; TNF-R, TNF receptor; TRAF, TNF receptor-associated factor; LT-βR, lymphotoxin-β receptor; HEK, human embryonic kidney; HVEM, herpesvirus entry mediator; SAPK, stress-activated protein kinase; JNK, c-Jun N-terminal kinase; NIK, NF-κB-inducing kinase; EMSA, electrophoretic mobility shift assay; mAb, monoclonal antibody; HA, hemagglutinin; PCR, polymerase chain reaction. superfamily and is expressed on T, B, and NK cells as a disulfide-linked homodimer (1Hintzen R.Q. de Jong R. Lens S.M.A. van Lier R.A.W. Immunol. Today. 1997; 15: 307-311Abstract Full Text PDF Scopus (152) Google Scholar). CD27 ligand (CD70) belongs to the TNF superfamily and is expressed on the surface of activated T and B cells. Cross-linking of CD27 along with a suboptimal dose of phytohemagglutinin, phorbol 12-myristate 13-acetate, anti-CD2, or anti-CD3 antibodies resulted in vigorous proliferation of T cells, indicating that CD27 transmits a co-stimulatory signal in T cells (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar). On the other hand, ligation of CD27 on B cells enhanced IgG production (3Kobata T. Jacquot S. Kozlowski S. Agematsu K. Schlossman S.F. Morimoto C. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 11249-11253Crossref PubMed Scopus (152) Google Scholar). These studies implicated the important roles of CD27/CD70 interaction in immunoregulation through T-T and T-B cell interactions. A recent report also demonstrated a critical role of CD27/CD70 interaction in T cell development (4Gravestein L.A. van Ewijk W. Ossendorp F. Borst J. J. Exp. Med. 1996; 184: 675-685Crossref PubMed Scopus (40) Google Scholar). Although biological function of CD27/CD70 interaction has been extensively investigated, the mechanism by which CD27 transmits the signal has been largely unknown, except for a previous study, which demonstrated involvement of the protein tyrosine kinase cascade (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar). TNF receptor-associated factors (TRAFs) have emerged as signal transducers for some members of the TNF-R superfamily (5Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Abstract Full Text PDF PubMed Scopus (927) Google Scholar, 6Cheng G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, 7Hu H.M. O'Rourke K. Boguski M.S. Dixit V.M. J. Biol. Chem. 1995; 269: 30069-30072Abstract Full Text PDF Google Scholar, 8Regnier C.H. Tomasetto C. Moog-Lutz C. Chenard M.-P. Wendling C. Basset P. Rio M.-C. J. Biol. Chem. 1995; 270: 25715-25721Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 9Nakano H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar). All TRAFs, except for TRAF1, are composed of N-terminal zinc RING finger, multiple zinc fingers, coiled-coil, and C-terminal receptor binding (TRAF) domains (5Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Abstract Full Text PDF PubMed Scopus (927) Google Scholar, 6Cheng G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, 9Nakano H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar, 11Mosialos G. Birkenbach M. Yalamanchili R. VanArsdale T. Ware C.F. Kieff E. Cell. 1995; 80: 389-399Abstract Full Text PDF PubMed Scopus (899) Google Scholar). Whereas an N-terminal RING finger domain of TRAF2, TRAF5, and TRAF6 is responsible for NF-κB activation, the TRAF and coiled-coil domains are required for homo- and heterodimerization and receptor association (5Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Abstract Full Text PDF PubMed Scopus (927) Google Scholar, 6Cheng G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, 9Nakano H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar, 12Rothe M. Sarma Dixit V.M. Goeddel D.V. Science. 1995; 269: PubMed Scopus Google Scholar). the of other have been to with the domain and H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 10Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Crossref PubMed Scopus (1112) Google Scholar, 12Rothe M. Sarma Dixit V.M. Goeddel D.V. Science. 1995; 269: PubMed Scopus Google Scholar, J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, T. S. S. T. K. S. T. G. Kieff E. T. J. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, S. H. T. R. M. K. Yagita H. Okumura K. J. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). TRAF2 has been to with domain and receptor via the H. Goeddel D.V. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, A.M. O'Rourke K. M. R. L. R. J. Dixit V.M. Science. 1996; PubMed Scopus Google Scholar, J. T. Goeddel D.V. R. Nature. 1996; PubMed Scopus Google Scholar). TRAF2, and TRAF5 also with protein the protein of G. Birkenbach M. Yalamanchili R. VanArsdale T. Ware C.F. Kieff E. Cell. 1995; 80: 389-399Abstract Full Text PDF PubMed Scopus (899) Google Scholar). TRAF2 also in the activation of stress-activated kinase (SAPK)/c-Jun N-terminal kinase induced by TNF H. Goeddel D.V. M. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, C. J. 1997; PubMed Scopus Google Scholar, G. A. A. C. M. Science. 1997; PubMed Scopus Google Scholar). and TRAF5 are involved in by G. Cleary A.M. Ye Z.-S. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Crossref PubMed Scopus (442) Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). has been also to involved in by G. Kieff E. Ware C.F. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google Scholar). The mechanism by which NF-κB to Recently, a kinase was that with TRAF2 and activates NF-κB-inducing kinase D. Nature. 1997; PubMed Scopus Google Scholar). the role of NIK in or NF-κB activation is CD27 is to other co-stimulatory and the herpesvirus entry M.S. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). was to with TRAF2 and TRAF5 M. M. A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. R. M. W.J. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). Here we demonstrate that CD27 activates both NF-κB and which are by TRAF2 and also demonstrate that a kinase-inactive mutant of NIK TRAF2-, and NF-κB and SAPK/JNK activation. These results a role of TRAF2 and TRAF5 in CD27 and that NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-κB and SAPK/JNK activation. have important roles of in through members of the TNF-R superfamily. we demonstrated that CD27 with TRAF2 and TRAF5, and are implicated in NF-κB and SAPK/JNK activation by CD27. results that other members of the TNF-R as and also with and NF-κB and SAPK/JNK also demonstrated that a kinase-inactive mutant NIK blocked and NF-κB activation, indicating that NIK is a common downstream kinase of TRAF2, TRAF5, and TRAF6 for NF-κB activation. studies H. Goeddel D.V. M. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, C.H. Goeddel D.V. M. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google that protein kinase responsible for and SAPK/JNK activation. Here we demonstrated that NIK also activates SAPK/JNK and a kinase-inactive mutant NIK SAPK/JNK activation by TRAF2, TRAF5, and CD27. The dominant negative of on SAPK/JNK activation by CD27 and to that on NF-κB activation. These results that other protein kinase kinase as protein kinase the dominant negative of on SAPK/JNK activation. The mechanism by which NIK activates SAPK/JNK is A previous that CD27 induced tyrosine of signal and the with a kinase blocked co-stimulatory signal through CD27 (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar). that CD27 activates is protein tyrosine and is the of which activates NF-κB and has been that CD27, LT-βR, and with both TRAF2 and TRAF5 H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, S. H. T. R. M. K. Yagita H. Okumura K. J. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar, M. M. A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. R. M. W.J. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). A common of through is the activation of NF-κB that by of a of TRAF in is involved in and proliferation in B cells J. Immunol. 1996; PubMed Google and CD27 IgG production in B cells (3Kobata T. Jacquot S. Kozlowski S. Agematsu K. Schlossman S.F. Morimoto C. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 11249-11253Crossref PubMed Scopus (152) Google Scholar). is involved in some of negative in the R. A. T. E. A. H. H. R. A. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google and is implicated in development R. van Ewijk W. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar, R. F. J. Exp. Med. 1996; 184: PubMed Scopus Google Scholar). The in in the in with the of as as for cells, which an important role in of and TRAF5 H. M. K. Ware C.F. Yagita H. Okumura K. 1997; PubMed Scopus Google or The of on receptor CD27. TRAF2 and TRAF5 have some in other the roles of TRAF2 and TRAF5 in TRAF5 with the and H. or R. J. 1997; Scopus Google Scholar). On the other hand, TRAF5 with TRAF2 These results that TRAF2 and TRAF5 through interaction with of downstream The recent of revealed that SAPK/JNK activation, NF-κB activation, by TNF is in A. D. J. F. A. de D. P. M. Goeddel D.V. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). results that a TRAF5 NF-κB activation by TNF, that TRAF2 and TRAF5 in NF-κB activation by SAPK/JNK activation by TRAF2 with a of TRAF2 to SAPK/JNK and TRAF2 to SAPK/JNK activation to TRAF2 and TRAF5 are in via CD27 and other members of the TNF-R in and have important roles of in through members of the TNF-R superfamily. we demonstrated that CD27 with TRAF2 and TRAF5, and are implicated in NF-κB and SAPK/JNK activation by CD27. results that other members of the TNF-R as and also with and NF-κB and SAPK/JNK also demonstrated that a kinase-inactive mutant NIK blocked and NF-κB activation, indicating that NIK is a common downstream kinase of TRAF2, TRAF5, and TRAF6 for NF-κB activation. studies H. Goeddel D.V. M. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, C.H. Goeddel D.V. M. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google that protein kinase responsible for and SAPK/JNK activation. Here we demonstrated that NIK also activates SAPK/JNK and a kinase-inactive mutant NIK SAPK/JNK activation by TRAF2, TRAF5, and CD27. The dominant negative of on SAPK/JNK activation by CD27 and to that on NF-κB activation. These results that other protein kinase kinase as protein kinase the dominant negative of on SAPK/JNK activation. The mechanism by which NIK activates SAPK/JNK is A previous that CD27 induced tyrosine of signal and the with a kinase blocked co-stimulatory signal through CD27 (2Kobata T. Agematsu K. Kameoka J. Schlossman S.F. Morimoto C. J. Immunol. 1994; 153: 5422-5432PubMed Google Scholar). that CD27 activates is protein tyrosine and is the of which activates NF-κB and has been that CD27, LT-βR, and with both TRAF2 and TRAF5 H. Oshima H. Chung W. Williams-Abbot L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, S. H. T. R. M. K. Yagita H. Okumura K. J. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, T. T. T. T. T. T. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar, M. M. A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. R. M. W.J. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). A common of through is the activation of NF-κB that by of a of TRAF in is involved in and proliferation in B cells J. Immunol. 1996; PubMed Google and CD27 IgG production in B cells (3Kobata T. Jacquot S. Kozlowski S. Agematsu K. Schlossman S.F. Morimoto C. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 11249-11253Crossref PubMed Scopus (152) Google Scholar). is involved in some of negative in the R. A. T. E. A. H. H. R. A. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google and is implicated in development R. van Ewijk W. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar, R. F. J. Exp. Med. 1996; 184: PubMed Scopus Google Scholar). The in in the in with the of as as for cells, which an important role in of and TRAF5 H. M. K. Ware C.F. Yagita H. Okumura K. 1997; PubMed Scopus Google or The of on receptor CD27. TRAF2 and TRAF5 have some in other the roles of TRAF2 and TRAF5 in TRAF5 with the and H. or R. J. 1997; Scopus Google Scholar). On the other hand, TRAF5 with TRAF2 These results that TRAF2 and TRAF5 through interaction with of downstream The recent of revealed that SAPK/JNK activation, NF-κB activation, by TNF is in A. D. J. F. A. de D. P. M. Goeddel D.V. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). results that a TRAF5 NF-κB activation by TNF, that TRAF2 and TRAF5 in NF-κB activation by SAPK/JNK activation by TRAF2 with a of TRAF2 to SAPK/JNK and TRAF2 to SAPK/JNK activation to TRAF2 and TRAF5 are in via CD27 and other members of the TNF-R in and and Kieff for also for
Akiba et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: