A Conserved Signal-responsive Sequence Mediates Activation-induced Alternative Splicing of CD45

Alternative splicing of nascent transcripts is a widespread mechanism for altering protein expression in response to extracellular stimuli. However, little is known about the sequences that mediate signal-induced alternative splicing, complicating efforts to identify genes whose splicing may be regulated in response to a particular stimuli. Here we define a sequence element that is both the primary determinant of CD45 variable exon exclusion following T cell stimulation by PMA and is sufficient to confer activation-induced skipping of a heterologous exon. Additionally, we show that this regulatory element has homology to sequences in other signal-regulated genes, suggesting that the alternative splicing of large families of genes may be regulated by common signaling pathways.