Abstract
Recent insight into the human genome has revealed that most genes encode multiple distinct protein isoforms through the process of alternative pre‐mRNA splicing. Recently we have identified ~150 genes that exhibit an alteration in isoform expression in response to T cell stimulation. Through detailed studies of the regulated splicing of the protein tyrosine phosphatase CD45, we have identified the regulatory sequence and proteins that control activation‐induced isoform expression of CD45 as well as exons in several other genes essential for T cell function. Much of the regulation of CD45 exon inclusion is controlled by the multifunctional proteins hnRNP L and PSF (PTB‐associated splicing factor). Studies into how these proteins mediate exon repression has lead to new insight into mechanisms of alternative splicing. Moreover, we have gained extensive insight into how the activity of PSF, in particular, is regulated by the GSK3 signaling pathway. Progress in our understanding of the regulation of splicing of CD45 and other T cell related genes will be presented.
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