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Effect Of Simulated Microgravity On Activated T Cell Gene TranscriptionStudies of T lymphocytes under the shear stress environment of clinorotation have demonstrated an inhibition of activation in response to TCR mediated signaling. These results mimic those observed during space flight. This work investigates the molecular signaling events of T lymphocyte activation with clinorotation. Purified human T lymphocytes and the T cell clone Jurkat exhibit an uncoupling of signaling as mediated through the TCR. Activation of the transcription factor AP-1 is inhibited while activation of NFAT occurs. NFAT dephosphorylation and activation is dependent on sustained Ca(++) influx. Alternatively, AP-1, which consists of two transcription factors, jun and fos, is activated by PKC and Ras mediated pathways. TCR signaling is known to be dependent on cytoskeletal rearrangements, in particular, raft aggregation is critical. Raft aggregation, as mediated through GM, crosslinking, overcomes the inhibition of T lymphocyte activation with clinorotation, indicating that the block is occurring upstream of raft aggregation. Clinorotation is shown to have an effect similar to a weak TCR signal.
Document ID
20030067910
Acquisition Source
Headquarters
Document Type
Other
Authors
Morrow, Maureen A.
(State Univ. of New York New Paltz, NY, United States)
Date Acquired
August 21, 2013
Publication Date
January 1, 2003
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: NAG2-1379
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.
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