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Molecular and Cellular Biology, October 1999, p. 6991-7000, Vol. 19, No. 10
Department of Biological Sciences, Columbia
University, New York, New York 10027,1
and Program in Molecular Biology and Cancer, Samuel
Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario,
Canada M5G 1X52
Received 24 May 1999/Returned for modification 8 July 1999/Accepted 21 July 1999
The splicing of mammalian mRNA precursors requires both protein
phosphorylation and dephosphorylation, likely involving modification of
members of the SR protein family of splicing factors. Several kinases
have been identified that can phosphorylate SR proteins in vitro, and
transfection assays have provided evidence that at least one of these,
Clk/Sty, can modulate splicing in vivo. But evidence that a specific
kinase can directly affect the splicing activity of SR proteins has
been lacking. Here, by using purified recombinant Clk/Sty, a
catalytically inactive mutant, and individual SR proteins, we show that
Clk/Sty directly affects the activity of SR proteins, but not other
essential splicing factors, in reconstituted splicing assays. We also
provide evidence that both hyper- and hypophosphorylation inhibit SR
protein splicing activity, repressing constitutive splicing and
switching alternative splice site selection. These findings indicate
that Clk/Sty directly and specifically influences the activity of SR
protein splicing factors and, importantly, show that both under- and
overphosphorylation of SR proteins can modulate splicing.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Protein Kinase Clk/Sty Directly Modulates SR Protein
Activity: Both Hyper- and Hypophosphorylation Inhibit
Splicing

*
Corresponding author. Mailing address: Department of
Biological Sciences, Columbia University, 1212 Amsterdam Ave., New
York, NY 10027. Phone: (212) 854-4647. Fax: (212) 865-8246. E-mail: jlm2{at}columbia.edu.
Present address: Department of Molecular and Medical Genetics,
University of Toronto, Toronto, Ontario, Canada M5S 1A8.
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