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Activation of c-jun N-terminal kinase by 4-1BB (CD137), a T cell co-stimulatory molecule.
Mol Cells. 2000 Jun 30; 10(3):247-52.MC

Abstract

It has been widely accepted that T cell activation requires two signals; one from the binding of the antigen/major histocompatibility complex to the T-cell receptor (TCR)/CD3 complex and the other from the interaction between a surface molecule on antigen presenting cells and its receptor on T cells. The second signal is considered as co-stimulatory and the B7/CD28 pair has been well studied as a prototype. Recently 4-1BB (CD137) has been characterized as another co-stimulatory molecule for T cell activation. However, unlike the CD28/B7 pair, 4-1BB and its ligand 4-1BBL constitute a member of the tumor necrosis factor (TNF) receptor/TNF pair superfamily. The signaling mechanism of 4-1BB has not been revealed in detail. To investigate whether 4-1BB takes the signaling pathways analogous to those for TNF receptors, we generated polyclonal antibodies against human 4-1BB and 4-1BBL and established stable transfectants of the receptor and the ligand with a high level of cell surface expression. Over-expression of h4-1BB was found to result in the activation of c-Jun N-terminal kinase (JNK) in the human embryonic kidney cell line 293. In T cells, it has been previously demonstrated that JNK activation requires dual signals such as the ligation of TCR/CD3 complex plus CD28 co-stimulation or PMA plus ionomycin. The JNK activation by 4-1BB in Jurkat T cells was also found to require stimulation of the TCR/CD3 complex, consistent with the notion that 4-1BB functions as a co-stimulatory molecule for T cell activation.

Authors+Show Affiliations

Department of Microbiology and Immunology, College of Dentistry, Chosun University, Kwangju, Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10901161

Citation

Kim, H H., et al. "Activation of C-jun N-terminal Kinase By 4-1BB (CD137), a T Cell Co-stimulatory Molecule." Molecules and Cells, vol. 10, no. 3, 2000, pp. 247-52.
Kim HH, Kwack K, Lee ZH. Activation of c-jun N-terminal kinase by 4-1BB (CD137), a T cell co-stimulatory molecule. Mol Cells. 2000;10(3):247-52.
Kim, H. H., Kwack, K., & Lee, Z. H. (2000). Activation of c-jun N-terminal kinase by 4-1BB (CD137), a T cell co-stimulatory molecule. Molecules and Cells, 10(3), 247-52.
Kim HH, Kwack K, Lee ZH. Activation of C-jun N-terminal Kinase By 4-1BB (CD137), a T Cell Co-stimulatory Molecule. Mol Cells. 2000 Jun 30;10(3):247-52. PubMed PMID: 10901161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of c-jun N-terminal kinase by 4-1BB (CD137), a T cell co-stimulatory molecule. AU - Kim,H H, AU - Kwack,K, AU - Lee,Z H, PY - 2000/7/20/pubmed PY - 2001/2/28/medline PY - 2000/7/20/entrez SP - 247 EP - 52 JF - Molecules and cells JO - Mol. Cells VL - 10 IS - 3 N2 - It has been widely accepted that T cell activation requires two signals; one from the binding of the antigen/major histocompatibility complex to the T-cell receptor (TCR)/CD3 complex and the other from the interaction between a surface molecule on antigen presenting cells and its receptor on T cells. The second signal is considered as co-stimulatory and the B7/CD28 pair has been well studied as a prototype. Recently 4-1BB (CD137) has been characterized as another co-stimulatory molecule for T cell activation. However, unlike the CD28/B7 pair, 4-1BB and its ligand 4-1BBL constitute a member of the tumor necrosis factor (TNF) receptor/TNF pair superfamily. The signaling mechanism of 4-1BB has not been revealed in detail. To investigate whether 4-1BB takes the signaling pathways analogous to those for TNF receptors, we generated polyclonal antibodies against human 4-1BB and 4-1BBL and established stable transfectants of the receptor and the ligand with a high level of cell surface expression. Over-expression of h4-1BB was found to result in the activation of c-Jun N-terminal kinase (JNK) in the human embryonic kidney cell line 293. In T cells, it has been previously demonstrated that JNK activation requires dual signals such as the ligation of TCR/CD3 complex plus CD28 co-stimulation or PMA plus ionomycin. The JNK activation by 4-1BB in Jurkat T cells was also found to require stimulation of the TCR/CD3 complex, consistent with the notion that 4-1BB functions as a co-stimulatory molecule for T cell activation. SN - 1016-8478 UR - https://www.unboundmedicine.com/medline/citation/10901161/Activation_of_c_jun_N_terminal_kinase_by_4_1BB__CD137__a_T_cell_co_stimulatory_molecule_ L2 - http://www.molcells.org/journal/view.html?year=2000&volume=10&number=3&spage=247 DB - PRIME DP - Unbound Medicine ER -