Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors

CD45 is a transmembrane glycoprotein possessing tyrosine phosphatase activi ty, which is involved in cell signaling. CD45 is expressed on the surface o f most leukocytes and can be alternatively spliced by the inclusion or skip ping of three variable exons (4, 5, and 6 or A, B, and C) to produce up to eight isoforms, In T cells, the splicing pattern of CD45 isoforms changes a fter activation; naive cells express high m.w. isoforms of CD45 which predo minantly express exon A (CD45RA), whereas activated cells lose expression o f exon A to form low m.w. isoforms of CD45 including CD45RO. Little is know n about the specific factors controlling the switch in CD45 splicing which occurs on activation. In this study, we examined the influence of the SR fa mily of splicing factors, which, like CD45, are expressed in tissue-specifi c patterns and have been shown to modulate the alternative splicing of a va riety of transcripts. We show that specific SR proteins have antagonistic e ffects on CD45 splicing, leading either to exon inclusion or skipping. Furt hermore, we were able to demonstrate specific changes in the SR protein exp ression pattern during T cell activation.