We have investigated transcription factor binding at the IL-2 promoter in activated T cells to examine the effect of modeled microgravity as achieved with clinorotation. We have definitively shown that modeled microgravity inhibits or decreases transcription factor binding of all transcription factors tested to date. This electrophoretic mobility shift analysis, with both Jurkat and purified human T cells, correlates with the previous data that has shown a loss of IL-2 transcription in response to modeled microgravity.
Most recently, we have been focusing our analysis on the NFAT
transcription factor. Binding at the NFAT promoter site is blocked by
modeled microgravity, but this binding is known to be dependent on the
AP-1 transcription factor. Western analysis suggests that that modeled
microgravity does not block the nuclear localization of this
transcription factor in response to activation. These results are
consistent with the theory that Ca++ dependent activation is not
inhibited by modeled microgravity, whereas the MAP kinase pathway
required to activate AP-1 may be targeted.
Publications
Morrow, M. (2006) Clinorotation Differentially Inhibits
T-Lymphocyte Transcription Factor Activation. In Vitro Cellular & Developmental
Biology-Animal, 42:153-158.
Morrow, M. and Ruszczyk (2001) Modeled Microgravity Blocks a Subset
of Signaling Pathways in Activated T cells. Scandinavian Journal of
Immunology 54(Sup1):18.
Morrow, M., Mayer, E. W., Perez, C. A. Adlman, M. and Siu, G.
(1999) Overexpression of the Helix-Loop-Helix Protein Id2 Blocks T cell
Development at Multiple Stages. Molecular Immunology, 36:491-503.
Oltz, E., Yancopoulos, G., Morrow, M., Rolink, A., Lee, G., Wong,
F., Kaplan K., Gilles, S., Melchers, F. and Alt, F. (1992) A Novel
Regulatory Myosin Light Chain Gene Distinguishes Pre-B Cell Subsets
and is IL-7 Inducible. EMBO J., 11:2759-2767.
Morrow, M., Oltz, E., Yancopoulos, G., Lee, G., Kincade, P.,
Gilles,
S., and Alt, F. (1992) IL-7 Induction of N-myc and c-myc Expression in
Murine Precursor B Lymphocytes. Genes & Dev. 6:61-70.
Yancopoulos, G., Oltz, E., Rathbun, G., Berman, J., Smith, R.,
Lansford, R., Rothman, P., Okada, A., Lee, G., Morrow, M., Kaplan, K.,
Prockop, S., and Alt, F. (1990) Isolation of coordinately regulated
genes
that are expressed in discrete stages of B-cell development. PNAS,
87:5759-5763.
Ferrier, P., Covey., L., Li, S., Suh, H., Malynn, B., Blackwell,
K.,
Morrow, M. and Alt, F. (1990) Normal recombination substrate VH to DJH
rearrangements in pre-B cells lines from scid mice. J. Exp. Med.
171:1909-1918.
Alt, F., Rathbun, G., Berman, J., Malynn, B., Morrow, M.,
Logtenberg, T., and Yancopoulos, G. (1989) B Cell Differentiation:
Development of Antibody Repertoires. Progress in Immunology,
7:351-360.
Alt, F., Ferrier, P., Malynn, B., Lutzker, S., Rothman, P., Berman,
J., Blackwell, K., Mellis, S., Pollock, R., Furley, A., Rathbun, G.,
Yancopoulos, G., Logtenberg, T., Morrow, M., Cook, W., Heinke, B., and
Suh, H. (1989) Control of Recombination Events During Lymphocyte
Differentiation: Heavy Chain Variable Region Gene Assembly and Heavy
Chain Class-switching. In: Molecular Basis of the Immune Response,
Ann. N.Y. Acad. Sci. 546:9-24.
Newspapers: Opinion, "Genome Research Opens Possibilities"
The Poughkeepsie Journal, July, 9, 2000.
Letter to the Editor, "The Basics at SUNY New Paltz", New York Daily
News, January 15, 1999.
Newsletters: Morrow, M., 2000 "Professor Cures Students of
the Writing Blues", Write to Learn Issue 3, Volume 1.
Morrow, M., 1997 "Importance of Writing-Intensive Courses", Write to
Learn Issue 1, Volume 1 (Writing Board Newsletter).
