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Molecular and Cellular Biology, January 2000, p. 70-80, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Model System for Activation-Induced Alternative Splicing of CD45 Pre-mRNA in T Cells Implicates Protein Kinase C and Ras

Kristen W. Lynch and Arthur Weiss*

Departments of Medicine and of Microbiology and Immunology and the Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143-0795

Received 22 July 1999/Returned for modification 25 August 1999/Accepted 30 September 1999

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 Ca2+ 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.

* Corresponding author. Mailing address: Departments of Medicine and of Microbiology and Immunology and the Howard Hughes Medical Institute, University of California, San Francisco, 3rd and Parnassus Ave., San Francisco, CA 94143-0795. Phone: (415) 476-1291. Fax: (415) 502-5081. E-mail: aweiss{at}itsa.ucsf.edu.

Molecular and Cellular Biology, January 2000, p. 70-80, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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