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Publication : Kinase suppressor of Ras 1 is required for full ERK activation in thymocytes but not for thymocyte selection.

First Author  Filbert EL Year  2010
Journal  Eur J Immunol Volume  40
Issue  11 Pages  3226-34
PubMed ID  20865788 Mgi Jnum  J:165920
Mgi Id  MGI:4838929 Doi  10.1002/eji.201040349
Citation  Filbert EL, et al. (2010) Kinase suppressor of Ras 1 is required for full ERK activation in thymocytes but not for thymocyte selection. Eur J Immunol 40(11):3226-34
abstractText  The scaffold protein kinase suppressor of Ras 1 (KSR1) is critical for efficient activation of ERK in a number of cell types. Consistent with this, we observed a defect in ERK activation in thymocytes that lack KSR1. Interestingly, we found that the defect was much greater after PMA stimulation than by CD3 activation. Since ERK activation is believed to be important for thymocyte development, we analyzed thymocyte selection in KSR1-deficient (KSR1(-/-) ) mice. We found that positive selection in two different TCR transgenic models, HY and AND, was normal. On the other hand, negative selection in the HY model was slightly impaired in KSR1(-/-) mice. However, a defect in negative selection was not apparent in the AND TCR model system or in an endogenous superantigen-mediated model of negative selection. These results suggest that, despite a requirement for KSR1 for full ERK activation in thymocytes, full and efficient ERK activation is not essential for the majority of thymocyte selection events.
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