A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras.

Abstract:

:Multiple isoforms of the protein tyrosine phosphatase CD45 are expressed on the surface of human T cells. Interestingly, the expression of these isoforms has been shown to vary significantly upon T-cell activation. In this report, we describe a novel cell line-based model system in which we can mimic the activation-induced alternative splicing of CD45 observed in primary T cells. Of the many proximal signaling events induced by T-cell stimulation, we show that activation of protein kinase C and activation of Ras are important for the switch toward the exclusion of CD45 variable exons, whereas events related to Ca(2+) flux are not. In addition, the ability of cycloheximide to block the activation-induced alternative splicing of CD45 suggests a requirement for de novo protein synthesis. We further demonstrate that sequences which have previously been implicated in the tissue-specific regulation of CD45 variable exons are likewise necessary and sufficient for activation-induced splicing. These results provide an initial understanding of the requirements for CD45 alternative splicing upon T-cell activation, and they confirm the importance of this novel cell line in facilitating a more detailed analysis of the activation-induced regulation of CD45 than has been previously possible.

journal_name

Mol Cell Biol

authors

Lynch KW,Weiss A

doi

10.1128/mcb.20.1.70-80.2000

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

70-80

issue

1

eissn

0270-7306

issn

1098-5549

journal_volume

20

pub_type

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