Key points are not available for this paper at this time.
Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-κB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-κB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling. Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-κB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-κB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling. The TNFR 1The abbreviations used are: TNFR, tumor necrosis factor receptor; PCR, polymerase chain reaction. 1The abbreviations used are: TNFR, tumor necrosis factor receptor; PCR, polymerase chain reaction. superfamily includes, among others, TNFR1, TNFR2, Fas, NGFR, CD40, and CD30 (1Smith C.A. Farrah T. Goodwin R.G. Cell. 1994; 76: 959-962Google Scholar). Receptors within this group share a similar extracellular domain architecture of multiple cysteine-rich repeats, each containing about 40 amino acids with six cysteines. However, no significant homology is found within the intracellular domains with the exception of the death domain shared by TNFR1, Fas, and Wsl-1 (DR3) (2Itoh N. Nagata S. J. Biol. Chem. 1993; 268: 10932-10937Google Scholar, 3Tartaglia L.A. Ayres T.M. Wong G.H.W. Goeddel D.V. Cell. 1993; 74: 845-853Google Scholar, 4Kitson J. Raven T. Jiang Y.P. Goeddel D.V. Giles K. Pun K.T. Grinham C.J. Brown R. Farrow S.N. Nature. 1996; 384: 372-375Google Scholar, 5Chinnaiyan A.M. O'Rourke K. Yu G.L. Lyons R.H. Gary M. Duan D.R. Xing L. Gentz R. Ni J. Dixit V.M. Science. 1996; 274: 990-992Google Scholar). Post-receptor signaling mechanisms utilized by the TNFR superfamily have recently begun to emerge with the discovery of two distinct classes of receptor-associated proteins.The death domain proteins TRADD, RIP, and FADD interact with the death domain of TNFR1 or Fas following ligand-mediated receptor aggregation (6Muzio M. Chinnaiyan A.M. Kischkel F.C. O'Rourke K. Shevchenko A. Ni J. Scaffidi C. Bretz J.D. Zhang M. Gentz R. Mann M. Krammer P.H. Peter M.E. Dixit V.M. Cell. 1996; 85: 817-827Google Scholar, 7Boldin M.P. Goncharov T.M. Goltsev Y.V. Wallach D. Cell. 1996; 85: 803-815Google Scholar, 8Fernandes-Alnemri T. Armstrong R.C. Krebs J. Srinivasula S.M. Wang L. Bullrich F. Fritz L.C. Trapani J.A. Tomaselli K.J. Litwack G. Alnemri E. Proc. Natl. Acad. Sci. 1996; 93: 7464-7469Google Scholar, 9Cheng G. Cleary A.M. Ye Z. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Google Scholar). The N-terminal death effector domain of FADD then recruits Caspase-8 (Flice/MACH), an ICE-like cysteine protease, to the receptor complex (6Muzio M. Chinnaiyan A.M. Kischkel F.C. O'Rourke K. Shevchenko A. Ni J. Scaffidi C. Bretz J.D. Zhang M. Gentz R. Mann M. Krammer P.H. Peter M.E. Dixit V.M. Cell. 1996; 85: 817-827Google Scholar, 7Boldin M.P. Goncharov T.M. Goltsev Y.V. Wallach D. Cell. 1996; 85: 803-815Google Scholar, 8Fernandes-Alnemri T. Armstrong R.C. Krebs J. Srinivasula S.M. Wang L. Bullrich F. Fritz L.C. Trapani J.A. Tomaselli K.J. Litwack G. Alnemri E. Proc. Natl. Acad. Sci. 1996; 93: 7464-7469Google Scholar). This process activates the apoptotic protease cascade and results in rapid onset of apoptosis.The second group of signaling molecules, the TRAF proteins, directly interact with TNFR2, CD40, CD30, and lymphotoxin-β receptor (9Cheng G. Cleary A.M. Ye Z. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Google Scholar, 10Hu M.H. O'Rourke K. Boguski M.S. Dixit V.M. J. Biol. Chem. 1994; 269: 300069-300072Google Scholar, 11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 12Lee S.Y. Lee S.Y. Kandala G. Liou M.L. Liou H.C. Choi Y. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 9699-9703Google Scholar). No obvious motifs are shared by the cytoplasmic regions of these TRAF-binding receptors except for a few conserved amino acids. Six TRAF proteins have been reported, each containing a highly conserved TRAF domain at the C terminus and, with the exception of TRAF1, a lesser conserved N-terminal RING finger and zinc finger motif (9Cheng G. Cleary A.M. Ye Z. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Google Scholar, 10Hu M.H. O'Rourke K. Boguski M.S. Dixit V.M. J. Biol. Chem. 1994; 269: 300069-300072Google Scholar, 11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 13Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Google Scholar, 14Regnier C.H. Tomasetto C. Moog-Lutz C. Chenard M.P. Wendling C. Basset P. Rio M.C. J. Biol. Chem. 1995; 270: 25715-25721Google Scholar, 15Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Google Scholar). Specific receptor recognition is mediated through the TRAF domain. Biological activities and post-receptor signaling mechanisms of the TRAF proteins are still obscure. TRAF2, TRAF5, and TRAF6, when overexpressed, activate NF-κB (11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 13Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Google Scholar, 16Rothe M. Sarma V. Dixit V.M. Goeddel D.V. Science. 1995; 269: 1424-1427Google Scholar). TRAF2 is also required for TNF-induced JNK activation (17Liu Z.G. Hsu H. Goeddel D.V. Karin M. Cell. 1996; 87: 565-576Google Scholar). The N-terminal RING finger motif is necessary for both of these activities.In the course of Amgen EST project, we discovered a novel TNFR-related protein we have named ATAR (anotherTRAF-associated receptor). Expression of ATAR is highly tissue-specific. To we the to for signaling proteins with the intracellular domain of ATAR. found ATAR with both TRAF2 and Like most other TRAF-binding TNFR family ATAR also NF-κB to a of a novel TNFR family member the Amgen EST a mouse a protein we ATAR a signal and a The extracellular domain cysteine-rich and is most to The receptor a cytoplasmic of only amino acids. the we also different in within the extracellular domain or of receptor However, of the cysteine repeats, suggesting in The human of the receptor a bone the mouse and human share and 25% within extracellular and intracellular of mouse ATAR in an the ATAR highly expressed in spleen, thymus, bone marrow, lung, and small intestine. of in and for human ATAR by not of ATAR. used in the of mouse the of we used to for signaling proteins interact with the ATAR intracellular domain. Human and mouse with containing the domain to the human ATAR intracellular domain. of 40 and TRAF5 or TRAF2. of these TRAF5 and TRAF2 a C-terminal TRAF with this domain receptor also the interaction of ATAR with and by interaction No interaction of ATAR with or in this with TRAF proteins. human and mouse ATAR interact with TRAF5 and TRAF2. Expression or of human or mouse ATAR intracellular domain to the domain with activation domain with TRAF1, TRAF2, or TRAF5 proteins. and and containing 20 the and also of also and a of TRAF-binding of human ATAR. conserved amino acids within the TRAF-binding of human and ATAR of the amino acids within ATAR with The intracellular domain containing each to the and the protein for interaction with TRAF2 and TRAF5 in the interaction the and also of human and mouse ATAR are conserved within intracellular we the of mouse ATAR to interact with TRAF proteins. Like human mouse ATAR with TRAF2 and TRAF5 but not or a of conserved amino acids in mouse and in among largely intracellular domains suggesting the of this conserved in TRAF To the TRAF-interacting we or of the human ATAR intracellular domain to the domain and interaction with TRAF proteins. The protein containing the conserved to both TRAF5 and TRAF2. the C-terminal 20 amino acids of ATAR for TRAF the of these amino acids are conserved in the TRAF-interacting of of and to the TRAF interaction G. Baltimore D. 1996; Scholar). of the conserved amino acids of ATAR with and each for interaction with TRAF2 and TRAF5 The to at ATAR interaction with the TRAF proteins. However, the other the receptor with TRAF2 and then the interaction of ATAR with TRAF proteins in the of ATAR with a TRAF2 or TRAF5 human each with or a the extracellular domain of ATAR. of the with a the and with ATAR ATAR is TRAF-interacting TNFR family of ATAR with TRAF2 and with the of for human ATAR and TRAF2 and with and or ATAR extracellular domain and TRAF proteins by with of ATAR with TRAF2 and TRAF5 and CD40, ATAR also NF-κB To this a with a ATAR in an of with the This NF-κB activation ATAR interaction with TRAF proteins, of the no with TRAF2 or TRAF5, to activate NF-κB activation by ATAR. activation of NF-κB in ATAR with of of and of or activities and the of The activities to for in of NF-κB activation by with of of of ATAR and the of and with to a of of activities synergistic activation of NF-κB by ATAR and TRAF5 with of of of of for TRAF5, or TRAF2, and to a of of activities similar protein in not TRAF2 and TRAF5, when overexpressed, activate NF-κB. This N-terminal RING finger and zinc finger motifs (11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 16Rothe M. Sarma V. Dixit V.M. Goeddel D.V. Science. 1995; 269: 1424-1427Google Scholar). a the RING and zinc finger a of with ATAR in NF-κB activation by ATAR overexpression when ATAR with TRAF2 RING and zinc finger not of both TRAF5 and TRAF2 in NF-κB activation the of TRAF5 and TRAF2 NF-κB we ATAR with TRAF5 or TRAF2 proteins in we found of ATAR and TRAF5 in a synergistic activation of NF-κB the no when ATAR with TRAF2 also a no with TRAF proteins. with TRAF5 or TRAF2, not NF-κB activation by TRAF5 or TRAF2 not This synergistic activation by ATAR and TRAF5 TRAF5 a in ATAR report the identification of a novel TNFR family ATAR is the member of this receptor superfamily The human and mouse are conserved with other members within the TNFR1, TNFR2, Fas, and share and in the two This is in the of the cytoplasmic However, we the distinct receptors two no other human with mouse and distinct receptors within this family share 25% each the both human and mouse ATAR intracellular domains interact with the TRAF proteins. This TRAF-binding resides in the C-terminal 20 amino acids of human is still to interact with within this is a of amino acids with the in the mouse amino have been to in by TNFR2, CD40, and This the of of ATAR in results in NF-κB This activation the interaction of ATAR with TRAF proteins, a TRAF-binding to activate NF-κB. we found of ATAR with TRAF5 but not TRAF2 in synergistic activation of NF-κB. results TRAF5 to NF-κB However, not of TRAF2 in this TRAF2 is expressed and not a factor in is to a recently protein a receptor for of and M.S. Cell. 1996; 87: Scholar). to this process activates ATAR and mediated by the receptor NF-κB the is of also with TRAF proteins through C-terminal cytoplasmic roles of ATAR and TRAF proteins in is mainly expressed in spleen, thymus, bone marrow, and small in are This ATAR a in or of the This is by the ATAR activation of NF-κB, in activates a of to Baltimore D. Cell. 1996; 87: Scholar). the known we not interaction of ATAR with and or not of of the of ATAR. The TNFR 1The abbreviations used are: TNFR, tumor necrosis factor receptor; PCR, polymerase chain reaction. 1The abbreviations used are: TNFR, tumor necrosis factor receptor; PCR, polymerase chain reaction. superfamily includes, among others, TNFR1, TNFR2, Fas, NGFR, CD40, and CD30 (1Smith C.A. Farrah T. Goodwin R.G. Cell. 1994; 76: 959-962Google Scholar). Receptors within this group share a similar extracellular domain architecture of multiple cysteine-rich repeats, each containing about 40 amino acids with six cysteines. However, no significant homology is found within the intracellular domains with the exception of the death domain shared by TNFR1, Fas, and Wsl-1 (DR3) (2Itoh N. Nagata S. J. Biol. Chem. 1993; 268: 10932-10937Google Scholar, 3Tartaglia L.A. Ayres T.M. Wong G.H.W. Goeddel D.V. Cell. 1993; 74: 845-853Google Scholar, 4Kitson J. Raven T. Jiang Y.P. Goeddel D.V. Giles K. Pun K.T. Grinham C.J. Brown R. Farrow S.N. Nature. 1996; 384: 372-375Google Scholar, 5Chinnaiyan A.M. O'Rourke K. Yu G.L. Lyons R.H. Gary M. Duan D.R. Xing L. Gentz R. Ni J. Dixit V.M. Science. 1996; 274: 990-992Google Scholar). Post-receptor signaling mechanisms utilized by the TNFR superfamily have recently begun to emerge with the discovery of two distinct classes of receptor-associated proteins. The death domain proteins TRADD, RIP, and FADD interact with the death domain of TNFR1 or Fas following ligand-mediated receptor aggregation (6Muzio M. Chinnaiyan A.M. Kischkel F.C. O'Rourke K. Shevchenko A. Ni J. Scaffidi C. Bretz J.D. Zhang M. Gentz R. Mann M. Krammer P.H. Peter M.E. Dixit V.M. Cell. 1996; 85: 817-827Google Scholar, 7Boldin M.P. Goncharov T.M. Goltsev Y.V. Wallach D. Cell. 1996; 85: 803-815Google Scholar, 8Fernandes-Alnemri T. Armstrong R.C. Krebs J. Srinivasula S.M. Wang L. Bullrich F. Fritz L.C. Trapani J.A. Tomaselli K.J. Litwack G. Alnemri E. Proc. Natl. Acad. Sci. 1996; 93: 7464-7469Google Scholar, 9Cheng G. Cleary A.M. Ye Z. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Google Scholar). The N-terminal death effector domain of FADD then recruits Caspase-8 (Flice/MACH), an ICE-like cysteine protease, to the receptor complex (6Muzio M. Chinnaiyan A.M. Kischkel F.C. O'Rourke K. Shevchenko A. Ni J. Scaffidi C. Bretz J.D. Zhang M. Gentz R. Mann M. Krammer P.H. Peter M.E. Dixit V.M. Cell. 1996; 85: 817-827Google Scholar, 7Boldin M.P. Goncharov T.M. Goltsev Y.V. Wallach D. Cell. 1996; 85: 803-815Google Scholar, 8Fernandes-Alnemri T. Armstrong R.C. Krebs J. Srinivasula S.M. Wang L. Bullrich F. Fritz L.C. Trapani J.A. Tomaselli K.J. Litwack G. Alnemri E. Proc. Natl. Acad. Sci. 1996; 93: 7464-7469Google Scholar). This process activates the apoptotic protease cascade and results in rapid onset of The second group of signaling molecules, the TRAF proteins, directly interact with TNFR2, CD40, CD30, and lymphotoxin-β receptor (9Cheng G. Cleary A.M. Ye Z. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Google Scholar, 10Hu M.H. O'Rourke K. Boguski M.S. Dixit V.M. J. Biol. Chem. 1994; 269: 300069-300072Google Scholar, 11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 12Lee S.Y. Lee S.Y. Kandala G. Liou M.L. Liou H.C. Choi Y. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 9699-9703Google Scholar). No obvious motifs are shared by the cytoplasmic regions of these TRAF-binding receptors except for a few conserved amino acids. Six TRAF proteins have been reported, each containing a highly conserved TRAF domain at the C terminus and, with the exception of TRAF1, a lesser conserved N-terminal RING finger and zinc finger motif (9Cheng G. Cleary A.M. Ye Z. Hong D.I. Lederman S. Baltimore D. Science. 1995; 267: 1494-1498Google Scholar, 10Hu M.H. O'Rourke K. Boguski M.S. Dixit V.M. J. Biol. Chem. 1994; 269: 300069-300072Google Scholar, 11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 13Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Google Scholar, 14Regnier C.H. Tomasetto C. Moog-Lutz C. Chenard M.P. Wendling C. Basset P. Rio M.C. J. Biol. Chem. 1995; 270: 25715-25721Google Scholar, 15Rothe M. Wong S.C. Henzel W.J. Goeddel D.V. Cell. 1994; 78: 681-692Google Scholar). Specific receptor recognition is mediated through the TRAF domain. Biological activities and post-receptor signaling mechanisms of the TRAF proteins are still obscure. TRAF2, TRAF5, and TRAF6, when overexpressed, activate NF-κB (11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 13Cao Z. Xiong J. Takeuchi M. Kurama T. Goeddel D.V. Nature. 1996; 383: 443-446Google Scholar, 16Rothe M. Sarma V. Dixit V.M. Goeddel D.V. Science. 1995; 269: 1424-1427Google Scholar). TRAF2 is also required for TNF-induced JNK activation (17Liu Z.G. Hsu H. Goeddel D.V. Karin M. Cell. 1996; 87: 565-576Google Scholar). The N-terminal RING finger motif is necessary for both of these the course of Amgen EST project, we discovered a novel TNFR-related protein we have named ATAR (anotherTRAF-associated receptor). Expression of ATAR is highly tissue-specific. To we the to for signaling proteins with the intracellular domain of ATAR. found ATAR with both TRAF2 and Like most other TRAF-binding TNFR family ATAR also NF-κB to a of a novel TNFR family member the Amgen EST a mouse a protein we ATAR a signal and a The extracellular domain cysteine-rich and is most to The receptor a cytoplasmic of only amino acids. the we also different in within the extracellular domain or of receptor However, of the cysteine repeats, suggesting in The human of the receptor a bone the mouse and human share and 25% within extracellular and intracellular of mouse ATAR in an the ATAR highly expressed in spleen, thymus, bone marrow, lung, and small intestine. of in and for human ATAR by not the of we used to for signaling proteins interact with the ATAR intracellular domain. Human and mouse with containing the domain to the human ATAR intracellular domain. of 40 and TRAF5 or TRAF2. of these TRAF5 and TRAF2 a C-terminal TRAF with this domain receptor also the interaction of ATAR with and by interaction No interaction of ATAR with or in this with TRAF proteins. human and mouse ATAR interact with TRAF5 and TRAF2. Expression or of human or mouse ATAR intracellular domain to the domain with activation domain with TRAF1, TRAF2, or TRAF5 proteins. and and containing 20 the and also of also and a of TRAF-binding of human ATAR. conserved amino acids within the TRAF-binding of human and ATAR of the amino acids within ATAR with The intracellular domain containing each to the and the protein for interaction with TRAF2 and TRAF5 in the interaction the and also of human and mouse ATAR are conserved within intracellular we the of mouse ATAR to interact with TRAF proteins. Like human mouse ATAR with TRAF2 and TRAF5 but not or a of conserved amino acids in mouse and in among largely intracellular domains suggesting the of this conserved in TRAF To the TRAF-interacting we or of the human ATAR intracellular domain to the domain and interaction with TRAF proteins. The protein containing the conserved to both TRAF5 and TRAF2. the C-terminal 20 amino acids of ATAR for TRAF the of these amino acids are conserved in the TRAF-interacting of of and to the TRAF interaction G. Baltimore D. 1996; Scholar). of the conserved amino acids of ATAR with and each for interaction with TRAF2 and TRAF5 The to at ATAR interaction with the TRAF proteins. However, the other the receptor with TRAF2 and then the interaction of ATAR with TRAF proteins in the of ATAR with a TRAF2 or TRAF5 human each with or a the extracellular domain of ATAR. of the with a the and with ATAR ATAR is TRAF-interacting TNFR family of ATAR with TRAF2 and with the of for human ATAR and TRAF2 and with and or ATAR extracellular domain and TRAF proteins by with of ATAR with TRAF2 and TRAF5 and CD40, ATAR also NF-κB To this a with a ATAR in an of with the This NF-κB activation ATAR interaction with TRAF proteins, of the no with TRAF2 or TRAF5, to activate NF-κB activation by ATAR. activation of NF-κB in ATAR with of of and of or activities and the of The activities to for in of NF-κB activation by with of of of ATAR and the of and with to a of of activities synergistic activation of NF-κB by ATAR and TRAF5 with of of of of for TRAF5, or TRAF2, and to a of of activities similar protein in not TRAF2 and TRAF5, when overexpressed, activate NF-κB. This N-terminal RING finger and zinc finger motifs (11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 16Rothe M. Sarma V. Dixit V.M. Goeddel D.V. Science. 1995; 269: 1424-1427Google Scholar). a the RING and zinc finger a of with ATAR in NF-κB activation by ATAR overexpression when ATAR with TRAF2 RING and zinc finger not of both TRAF5 and TRAF2 in NF-κB activation the of TRAF5 and TRAF2 NF-κB we ATAR with TRAF5 or TRAF2 proteins in we found of ATAR and TRAF5 in a synergistic activation of NF-κB the no when ATAR with TRAF2 also a no with TRAF proteins. with TRAF5 or TRAF2, not NF-κB activation by TRAF5 or TRAF2 not This synergistic activation by ATAR and TRAF5 TRAF5 a in ATAR signaling. to a of a novel TNFR family member the Amgen EST a mouse a protein we ATAR a signal and a The extracellular domain cysteine-rich and is most to The receptor a cytoplasmic of only amino acids. the we also different in within the extracellular domain or of receptor However, of the cysteine repeats, suggesting in The human of the receptor a bone the mouse and human share and 25% within extracellular and intracellular of mouse ATAR in an the ATAR highly expressed in spleen, thymus, bone marrow, lung, and small intestine. of in and for human ATAR by not To the of we used to for signaling proteins interact with the ATAR intracellular domain. Human and mouse with containing the domain to the human ATAR intracellular domain. of 40 and TRAF5 or TRAF2. of these TRAF5 and TRAF2 a C-terminal TRAF with this domain receptor also the interaction of ATAR with and by interaction No interaction of ATAR with or in this human and mouse ATAR are conserved within intracellular we the of mouse ATAR to interact with TRAF proteins. Like human mouse ATAR with TRAF2 and TRAF5 but not or a of conserved amino acids in mouse and in among largely intracellular domains suggesting the of this conserved in TRAF To the TRAF-interacting we or of the human ATAR intracellular domain to the domain and interaction with TRAF proteins. The protein containing the conserved to both TRAF5 and TRAF2. the C-terminal 20 amino acids of ATAR for TRAF the of these amino acids are conserved in the TRAF-interacting of of and to the TRAF interaction G. Baltimore D. 1996; Scholar). of the conserved amino acids of ATAR with and each for interaction with TRAF2 and TRAF5 The to at ATAR interaction with the TRAF proteins. However, the other the receptor with TRAF2 and then the interaction of ATAR with TRAF proteins in the of ATAR with a TRAF2 or TRAF5 human each with or a the extracellular domain of ATAR. of the with a the and with ATAR ATAR is TRAF-interacting TNFR family of ATAR with TRAF2 and TRAF5 and CD40, ATAR also NF-κB To this a with a ATAR in an of with the This NF-κB activation ATAR interaction with TRAF proteins, of the no with TRAF2 or TRAF5, to activate NF-κB TRAF2 and TRAF5, when overexpressed, activate NF-κB. This N-terminal RING finger and zinc finger motifs (11Nakano H. Oshima H. Chung W. Williams-Abbott L. Ware C.F. Yagita H. Okumura K. J. Biol. Chem. 1996; 271: 14661-14664Google Scholar, 16Rothe M. Sarma V. Dixit V.M. Goeddel D.V. Science. 1995; 269: 1424-1427Google Scholar). a the RING and zinc finger a of with ATAR in NF-κB activation by ATAR overexpression when ATAR with TRAF2 RING and zinc finger not of both TRAF5 and TRAF2 in NF-κB activation To the of TRAF5 and TRAF2 NF-κB we ATAR with TRAF5 or TRAF2 proteins in we found of ATAR and TRAF5 in a synergistic activation of NF-κB the no when ATAR with TRAF2 also a no with TRAF proteins. with TRAF5 or TRAF2, not NF-κB activation by TRAF5 or TRAF2 not This synergistic activation by ATAR and TRAF5 TRAF5 a in ATAR signaling. report the identification of a novel TNFR family ATAR is the member of this receptor superfamily The human and mouse are conserved with other members within the TNFR1, TNFR2, Fas, and share and in the two This is in the of the cytoplasmic However, we the distinct receptors two no other human with mouse and distinct receptors within this family share 25% each the both human and mouse ATAR intracellular domains interact with the TRAF proteins. This TRAF-binding resides in the C-terminal 20 amino acids of human is still to interact with within this is a of amino acids with the in the mouse amino have been to in by TNFR2, CD40, and This the of of ATAR in results in NF-κB This activation the interaction of ATAR with TRAF proteins, a TRAF-binding to activate NF-κB. we found of ATAR with TRAF5 but not TRAF2 in synergistic activation of NF-κB. results TRAF5 to NF-κB However, not of TRAF2 in this TRAF2 is expressed and not a factor in is to a recently protein a receptor for of and M.S. Cell. 1996; 87: Scholar). to this process activates ATAR and mediated by the receptor NF-κB the is of also with TRAF proteins through C-terminal cytoplasmic roles of ATAR and TRAF proteins in is mainly expressed in spleen, thymus, bone marrow, and small in are This ATAR a in or of the This is by the ATAR activation of NF-κB, in activates a of to Baltimore D. Cell. 1996; 87: Scholar). the known we not interaction of ATAR with and or not of of the of ATAR. report the identification of a novel TNFR family ATAR is the member of this receptor superfamily The human and mouse are conserved with other members within the TNFR1, TNFR2, Fas, and share and in the two This is in the of the cytoplasmic However, we the distinct receptors two no other human with mouse and distinct receptors within this family share 25% each the both human and mouse ATAR intracellular domains interact with the TRAF proteins. This TRAF-binding resides in the C-terminal 20 amino acids of human is still to interact with within this is a of amino acids with the in the mouse amino have been to in by TNFR2, CD40, and This the of of ATAR in results in NF-κB This activation the interaction of ATAR with TRAF proteins, a TRAF-binding to activate NF-κB. we found of ATAR with TRAF5 but not TRAF2 in synergistic activation of NF-κB. results TRAF5 to NF-κB However, not of TRAF2 in this TRAF2 is expressed and not a factor in ATAR is to a recently protein a receptor for of and M.S. Cell. 1996; 87: Scholar). to this process activates ATAR and mediated by the receptor NF-κB the is of also with TRAF proteins through C-terminal cytoplasmic roles of ATAR and TRAF proteins in ATAR is mainly expressed in spleen, thymus, bone marrow, and small in are This ATAR a in or of the This is by the ATAR activation of NF-κB, in activates a of to Baltimore D. Cell. 1996; 87: Scholar). the known we not interaction of ATAR with and or not of of the of ATAR. members in the Amgen EST significant to this
Hsu et al. (Thu,) studied this question.