Editors' ChoiceAlternative Splicing

Spliced to Order

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Science's STKE  17 Dec 2002:
Vol. 2002, Issue 163, pp. tw479-TW479
DOI: 10.1126/stke.2002.163.tw479

Alternative splicing of genes is one way in which humans generate more complex biological systems from a set of genes only slightly larger than that of worms or flies. Such splicing can be regulated in response to activated signaling pathways, and Matter et al. now propose a mechanism by which mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 control splicing of the CD44 protein, a transmembrane receptor that binds hyaluronic acid. They found that the protein SAM68 (Src-associated in mitosis) bound to a splice regulatory element in the CD44 RNA. SAM68 also showed a shift in apparent molecular size during gel electrophoresis when isolated from cells in which ERK protein kinases were active, and recombinant ERK2 phosphorylated SAM68 fusion protein with glutathione in vitro. Results from in vitro splicing reactions provided further support for direct regulation of SAM68 by ERKs. GST-SAM68 that had been phosphorylated by ERK2 promoted splicing whereas unphosphorylated SAM68 had little effect. When expression of SAM68 was reduced in cells expressing morpholino antisense molecules, regulation of splicing through the ERK signaling pathway was diminished. The authors propose that SAM68 is a regulator of splicing that can be modulated in response to MAPK-mediated signals.

N. Matter, P. Herrlich, H. König, Singal-dependent regulation of splicing via phosphorylation of Sam68. Nature 420, 691-695 (2002). [Online Journal]

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