Defective survival and activation of thymocytes in transgenic mice expressing a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV

Molecular Endocrinology
K A AndersonA R Means

Abstract

We have generated transgenic mice that express a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) specifically in thymic T cells. The presence of this protein results in a markedly reduced thymic cellularity, although the distribution of the remaining cells is normal based on evaluation of the CD4 and CD8 cell surface antigens that are used to gauge T cell development. Isolated thymic T cells from the transgenic mice also show a dramatically decreased survival rate when evaluated in culture under conditions that do not favor activation. When challenged with an activating stimulus such as alpha-CD3 or a combination of phorbol ester plus ionophore, the cells are severely compromised in their ability to produce the cytokine interleukin-2 (IL-2). Reduction of IL-2 production is secondary to the inability to phosphorylate the cAMP response element binding protein, CREB, and induce expression of the immediate early genes such as Fos B that are required to transactivate the IL-2 promoter. Because transgene expression was regulated by the proximal promoter of the murine lck gene and this promoter is inactivated in T cells that exit the thymus, the mutant hCaMKIV is not present in peripheral T cells. C...Continue Reading

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Citations

Dec 12, 2001·Molecular and Cellular Biology·Kristin A Anderson, Anthony R Means
Aug 6, 2011·Journal of Leukocyte Biology·Ellen C TengAnthony R Means
Jun 18, 2002·Journal of Neurochemistry·Barbara Tremper-WellsMary Lou Vallano
Jan 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·V SéeJ P Loeffler
May 29, 2020·Antioxidants & Redox Signaling·Tsuyoshi TakataYasuo Watanabe
Jan 1, 2004·The Journal of Biological Chemistry·Shannon M LemrowAnthony R Means
Jul 16, 2005·The Journal of Biological Chemistry·Christine M KitsosAnthony R Means
Jul 10, 2001·The Journal of Biological Chemistry·V Sée, J P Loeffler
Nov 30, 2000·The Journal of Biological Chemistry·E E Corcoran, A R Means
May 1, 2021·International Journal of Molecular Sciences·Kinga SałaciakKarolina Pytka
Jan 27, 1999·Biochimica Et Biophysica Acta·J Krebs
Jun 23, 2009·Biochemical and Biophysical Research Communications·Kelie M ReeceBrian E Wadzinski

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