Specific Splice Signals

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Science  17 Aug 2001:
Vol. 293, Issue 5533, pp. 1225
DOI: 10.1126/science.293.5533.1225c

The generation of different proteins from a single gene by alternative splicing is regulated in a time-and tissue-specific manner. Although initiated by extracellular signals, transmission of such information from the cell surface to nuclear splicing machinery is not fully understood.

Now Weg-Remers et al. have made some progress by looking at the expression of variant isoforms of CD44 on the surface of T cells. Activation of primary T cells initiated the ERK, JNK, and p38 MAP kinase signaling cascades. However, only activation of the Ras-ERK pathway was needed to generate a mature form of CD44 that included a particular exon. Mutation of the splice-responsive elements within this exon reduced expression of the CD44 isoform in response to ERK activation. Splicing did not depend on protein synthesis, suggesting that posttranslational modification of regulatory splice factors, possibly by phosphorylation, may regulate splicing. The specificity of exon selection could thus be determined in part by the activation of distinct signaling pathways. — LC

EMBO J.20, 4194 (2001).

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