The Journal of Immunology, Vol 156, Issue 2 549-557, Copyright © 1996 by American Association of Immunologists

ARTICLES

pim-1 proto-oncogene expression in anti-CD3-mediated T cell activation is associated with protein kinase C activation and is independent of Raf-1

D Wingett, A Long, D Kelleher and NS Magnuson
Department of Veterans Affairs, Boise, ID 83702, USA.

We have studied pim-1 proto-oncogene expression in human T cell responses to Ag receptor-generated signals. The pim-1 gene encodes a serine/threonine protein kinase that is expressed primarily in cells of hematopoietic lineage and is implicated in the intracellular signaling processes accompanying lymphocyte activation. We show here that pim-1 mRNA expression is rapidly induced after receptor cross-linking with anti-CD3 Abs. We examined the linkage of pim-1 expression to known signaling pathways generated through the T cell Ag receptor. pim-1 mRNA was not substantially induced after elevation of intracellular free Ca2+. In contrast, PMA, which directly activates PKC, induced rapid pim- 1 expression. Further, anti-CD3- or PMA-induced pim-1 expression was markedly reduced by various PKC inhibitors and by deficiency of the PKC epsilon isoform in a mutant T cell line. Thus, T cell Ag receptor- linked pim-1 expression appears to be coupled to the PKC component of transmembrane signaling. Because the activation of protein kinase C has been shown to activate Raf-1 kinase activity, the involvement of Raf-1 in pim-1 expression was also investigated using a human T cell line stably transfected with an inducible Raf expression vector. Although the overexpression of activated Raf was shown to cause a substantial increase in IL-2 expression, no discernible effects on pim-1 were apparent. In addition, we examined transcriptional and post- transcriptional mechanisms involved in PKC-mediated pim-1 expression and observed that both transcriptional and post-transcriptional mechanisms are coordinately involved in the up-regulation of the pim-1 proto-oncogene.

This article has been cited by other articles:

				H. Mikkers, M. Nawijn, J. Allen, C. Brouwers, E. Verhoeven, J. Jonkers, and A. Berns Mice Deficient for All PIM Kinases Display Reduced Body Size and Impaired Responses to Hematopoietic Growth Factors Mol. Cell. Biol., July 1, 2004; 24(13): 6104 - 6115. [Abstract] [Full Text] [PDF]

				T. J. Mitchell, S. J. Whittaker, and S. John Dysregulated Expression of COOH-Terminally Truncated Stat5 and Loss of IL2-Inducible Stat5-Dependent Gene Expression in Sezary Syndrome Cancer Res., December 15, 2003; 63(24): 9048 - 9054. [Abstract] [Full Text] [PDF]

				J. A. Losman, X. P. Chen, B. Q. Vuong, S. Fay, and P. B. Rothman Protein Phosphatase 2A Regulates the Stability of Pim Protein Kinases J. Biol. Chem., February 7, 2003; 278(7): 4800 - 4805. [Abstract] [Full Text] [PDF]

				E.-M. Rainio, J. Sandholm, and P. J. Koskinen Cutting Edge: Transcriptional Activity of NFATc1 Is Enhanced by the Pim-1 Kinase J. Immunol., February 15, 2002; 168(4): 1524 - 1527. [Abstract] [Full Text] [PDF]

				N. Zhu, L. M. Ramirez, R. L. Lee, N. S. Magnuson, G. A. Bishop, and M. R. Gold CD40 Signaling in B Cells Regulates the Expression of the Pim-1 Kinase Via the NF-{kappa}B Pathway J. Immunol., January 15, 2002; 168(2): 744 - 754. [Abstract] [Full Text] [PDF]

				K. E. Borg, M. Zhang, D. Hegge, R. L. Stephen, D. J. Buckley, N. S. Magnuson, and A. R. Buckley Prolactin Regulation of pim-1 Expression: Positive and Negative Promoter Elements Endocrinology, December 1, 1999; 140(12): 5659 - 5668. [Abstract] [Full Text]

				M. Koshiba, S. Apasov, V. Sverdlov, P. Chen, L. Erb, J. T. Turner, G. A. Weisman, and M. V. Sitkovsky Transient up-regulation of P2Y2 nucleotide receptor mRNA expression is an immediate early gene response in activated thymocytes PNAS, February 4, 1997; 94(3): 831 - 836. [Abstract] [Full Text] [PDF]