HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahn, H.-J. Articles by Fujiwara, H. Search for Related Content PubMed PubMed Citation Articles by Ahn, H.-J. Articles by Fujiwara, H.

Requirement for Distinct Janus Kinases and STAT Proteins in T Cell Proliferation Versus IFN- Production Following IL-12 Stimulation¹

Biomedical Research Center, Osaka University Medical School, Yamada-oka, Suita, Osaka, Japan

While IL-12 is known to activate JAK2 and TYK2 and induce the phosphorylation of STAT4 and STAT3, little is known regarding how the activation of these signaling molecules is related to the biologic effects of IL-12. Using an IL-12-responsive T cell clone (2D6), we investigated their requirements for proliferation and IFN- production of 2D6 cells. 2D6 cells could be maintained with either IL-12 or IL-2. 2D6 lines maintained with IL-12 (2D6^IL-12) or IL-2 (2D6^IL-2) exhibited comparable levels of proliferation, but produced large or only small amounts of IFN-, respectively, when restimulated with IL-12 after starvation of either cytokine. 2D6^IL-12 induced TYK2 and STAT4 phosphorylation. In contrast, their phosphorylation was marginally induced in 2D6^IL-2. The reduced STAT4 phosphorylation was due to a progressive decrease in the amount of STAT4 protein along with the passages in IL-2-containing medium. 2D6^IL-12 and 2D6^IL-2 similarly proliferating in response to IL-12 induced comparable levels of JAK2 activation and STAT5 phosphorylation. JAK2 was associated with STAT5, and IL-12-induced STAT5 phosphorylation was elicited in the absence of JAK3 activation. These results indicate that IL-12 has the capacity to induce/maintain STAT4 and STAT5 proteins, and that TYK2 and JAK2 activation correlate with STAT4 phosphorylation/IFN- induction and STAT5 phosphorylation/cellular proliferation, respectively.

This article has been cited by other articles:

				V. Paunovic, H. P. Carroll, K. Vandenbroeck, and M. Gadina Signalling, inflammation and arthritis: Crossed signals: the role of interleukin (IL)-12, -17, -23 and -27 in autoimmunity Rheumatology, June 1, 2008; 47(6): 771 - 776. [Abstract] [Full Text] [PDF]

				T. Yoshimoto, M. Furuhata, S. Kamiya, M. Hisada, H. Miyaji, Y. Magami, K. Yamamoto, H. Fujiwara, and J. Mizuguchi Positive Modulation of IL-12 Signaling by Sphingosine Kinase 2 Associating with the IL-12 Receptor {beta}1 Cytoplasmic Region J. Immunol., August 1, 2003; 171(3): 1352 - 1359. [Abstract] [Full Text] [PDF]

				R. Nishikomori, T. Usui, C.-Y. Wu, A. Morinobu, J. J. O'Shea, and W. Strober Activated STAT4 Has an Essential Role in Th1 Differentiation and Proliferation That Is Independent of Its Role in the Maintenance of IL-12R{beta}2 Chain Expression and Signaling J. Immunol., October 15, 2002; 169(8): 4388 - 4398. [Abstract] [Full Text] [PDF]

				L. Burdelya, R. Catlett-Falcone, A. Levitzki, F. Cheng, L. B. Mora, E. Sotomayor, D. Coppola, J. Sun, S. Sebti, W. S. Dalton, et al. Combination Therapy with AG-490 and Interleukin 12 Achieves Greater Antitumor Effects than Either Agent Alone Mol. Cancer Ther., September 1, 2002; 1(11): 893 - 899. [Abstract] [Full Text] [PDF]

				C.-S. Park, Y.-F. Yang, X.-Y. Zhou, K. Toyooka, Y. Yashiro-Ohtani, W.-R. Park, M. Tomura, X.-G. Tai, T. Hamaoka, and H. Fujiwara Reversible CD8 expression induced by common cytokine receptor {gamma} chain-dependent cytokines in a cloned CD4+ Th1 cell line Int. Immunol., March 1, 2002; 14(3): 259 - 266. [Abstract] [Full Text] [PDF]

				M. Nakahira, H.-J. Ahn, W.-R. Park, P. Gao, M. Tomura, C.-S. Park, T. Hamaoka, T. Ohta, M. Kurimoto, and H. Fujiwara Synergy of IL-12 and IL-18 for IFN-{gamma} Gene Expression: IL-12-Induced STAT4 Contributes to IFN-{gamma} Promoter Activation by Up-Regulating the Binding Activity of IL-18-Induced Activator Protein 1 J. Immunol., February 1, 2002; 168(3): 1146 - 1153. [Abstract] [Full Text] [PDF]

				M. Nakahira, M. Tomura, M. Iwasaki, H.-J. Ahn, Y. Bian, T. Hamaoka, T. Ohta, M. Kurimoto, and H. Fujiwara An Absolute Requirement for STAT4 and a Role for IFN-{gamma} as an Amplifying Factor in IL-12 Induction of the Functional IL-18 Receptor Complex J. Immunol., August 1, 2001; 167(3): 1306 - 1312. [Abstract] [Full Text] [PDF]

				C. E. Verhagen, T. de Boer, H. H. Smits, F. A.W. Verreck, E. A. Wierenga, M. Kurimoto, D. A. Lammas, D. S. Kumararatne, O. Sanal, F. P. Kroon, et al. Residual Type 1 Immunity in Patients Genetically Deficient for Interleukin 12 Receptor {beta}1 (IL-12R{beta}1): Evidence for an IL-12R{beta}1-Independent Pathway of IL-12 Responsiveness in Human T Cells J. Exp. Med., August 21, 2000; 192(4): 517 - 528. [Abstract] [Full Text] [PDF]

				K. S. Wang, D. A. Frank, and J. Ritz Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4 Blood, May 15, 2000; 95(10): 3183 - 3190. [Abstract] [Full Text] [PDF]