CD45
/ LCA / B220 exist in multiple isoforms ranging
from 180 to 220 kDa, depending on alternative splicing of exons 4, 5, and
6. The corresponding protein domains are characterized by the binding of
mAbs specific for :
-
CD45RA (containing exon 4), which is expressed
by medullary thymocytes and naive/resting peripheral CD4+
T lymphocytes
-
CD45RB (containing exon 5)
-
CD45RC (containing exon 6)
-
CD45RO (exons 4 to 6 spliced out), which is
expressed by cortical thymocytes, CD4+ memory T lymphocyte subset
and activated T lymphocytes.
The activation-responsive sequence (ARS) is
required for the exclusion of exons 4, 5 and 6 from CD45 after stimulation
with PMA, which also induces alternative splicing in CTLA-4, agrin and
FYN genesref.
CD45 alternative splicing is regulated by cooperative action of the splice
factor U2AF1L4
/ U2AF26 and the transcription factor Gfi1.
U2AF26 promoted formation of the less-active CD45RO by facilitating exon
exclusion. Gfi1 antagonized that process by directly interacting with U2AF26,
identifying a previously unknown link between a transcription factor and
alternative splicing. The presence of Gfi1 led to formation of the more-active
CD45RB, whereas loss of Gfi1 favored CD45RO production. The relative abundance
of U2AF26 and Gfi1 determines the ratio of CD45 isoforms, thereby regulating
T cell activationref. |
thymocytes and CD4+
T lymphocytes |
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Copyright © 2001-2014 Daniele Focosi.
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