C-Jun Nh2-Terminal Kinase (Jnk)1 and Jnk2 Have Similar and Stage-Dependent Roles in Regulating T Cell Apoptosis and Proliferation

• DOI: 10.1084/jem.193.3.317
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Kanaga Sabapathy; Tuula Kallunki; Jean-Pierre David; Isabella Graef; Michael Karin; Erwin F. Wagner
• Keywords: 0301 basic medicine; T-Lymphocytes/cytology; CD3 Complex; Cell Survival; Knockout; T-Lymphocytes; Apoptosis; Inbred C57BL; Lymphocyte Activation; CD3 Complex/immunology; Mice; 03 medical and health sciences; Animals; Mitogen-Activated Protein Kinase 9; Transcription Factors/metabolism; Mitogen-Activated Protein Kinase 8; Phosphorylation; Mice, Knockout; B-Lymphocytes; DNA-Binding Proteins/metabolism; NFATC Transcription Factors; Nuclear Proteins; B-Lymphocytes/immunology; Cell Differentiation; Mitogen-Activated Protein Kinases/genetics; DNA-Binding Proteins; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Cell Division; Transcription Factors

Apoptotic and mitogenic stimuli activate c-Jun NH2-terminal kinases (JNKs) in T cells. Although T cells express both JNK1 and JNK2 isozymes, the absence of JNK2 alone can result in resistance to anti-CD3–induced thymocyte apoptosis and defective mature T cell proliferation. Similar defects in thymocyte apoptosis and mature T cell proliferation, the latter due to reduced interleukin 2 production, are also caused by JNK1 deficiency. Importantly, T cell function was compromised in Jnk1+/−Jnk2+/− double heterozygous mice, indicating that JNK1 and JNK2 play similar roles in regulating T cell function. The reduced JNK dose results in defective c-Jun NH2-terminal phosphorylation in thymocytes but not in peripheral T cells, in which nuclear factors of activated T cells (NK-ATs)–DNA binding activity is affected. Thus, JNK1 and JNK2 control similar functions during T cell maturation through differential targeting of distinct substrates.