The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2.
CD27 is a lymphocyte-specific member of the TNF receptor (TNFR) family. It is a costimulatory molecule for peripheral T cells, as defined by its ability to enhance the TCR-induced proliferative response. We show here that CD27 augments TCR-induced Jun N-terminal kinase (JNK) activity in primary murine lymph node T cells. To investigate how CD27 couples to JNK, we performed a yeast two hybrid screen with the CD27 cytoplasmic tail. This revealed that CD27 directly associates with Traf-2. Transfection experiments using dominant negative Traf-2 indicated that CD27 communicates with JNK via Traf-2. These findings group CD27 together with other members of the TNFR family, TNFR-1, -2, CD30 and CD40, which have all been shown to couple to Traf proteins. Since Traf proteins have been reported to initiate an anti-apoptotic signaling pathway, our data suggest that CD27 not only regulates proliferation, but also survival of T lymphocytes.
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
L A
LA
Gravestein
D
D
Amsen
M
M
Boes
C R
CR
Calvo
A M
AM
Kruisbeek
J
J
Borst
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases; D011494:Protein Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D047992:TNF Receptor-Associated Factor 2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*
D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases