tailieunhanh - Báo cáo khoa học: Phosphorylation mechanism and structure of serine-arginine protein kinases

The splicing of mRNA requires a group of essential factors known as SR proteins, which participate in the maturation of the spliceosome. These proteins contain one or two RNA recognition motifs and a C-terminal domain rich in Arg-Ser repeats (RS domain). | IFEBS Journal REVIEW ARTICLE Phosphorylation mechanism and structure of serine-arginine protein kinases Gourisankar Ghosh1 and Joseph A. Adams2 1 Department of Chemistry and Biochemistry University of California San Diego La Jolla CA USA 2 Department of Pharmacology University of California San Diego La Jolla CA USA Keywords mechanism protein kinase splicing SR protein structure Correspondence J. A. Adams Department of Pharmacology University of California San Diego La Jolla CA 92093-0636 USA Fax 1 858 822 3361 Tel 1 858 822 3360 E-mail j2adams@ Received 7 July 2010 revised 9 November 2010 accepted 10 December 2010 doi The splicing of mRNA requires a group of essential factors known as SR proteins which participate in the maturation of the spliceosome. These proteins contain one or two RNA recognition motifs and a C-terminal domain rich in Arg-Ser repeats RS domain . SR proteins are phosphorylated at numerous serines in the RS domain by the SR-specific protein kinase SRPK family of protein kinases. RS domain phosphorylation is necessary for entry of SR proteins into the nucleus and may also play important roles in alternative splicing mRNA export and other processing events. Although SR proteins are polyphosphorylated in vivo the mechanism underlying this complex reaction has only been recently elucidated. Human alternative splicing factor serine arginine-rich splicing factor 1 SRSF1 a prototype for the SR protein family is regiospecifically phosphorylated by SRPK1 a post-translational modification that controls cytoplasmic-nuclear localization. SRPK1 binds SRSF1 with unusually high affinity and rapidly modifies about 10-12 serines in the N-terminal region of the RS domain RS1 using a mechanism that incorporates sequential C-terminal to N-terminal phosphorylation and several processive steps. SRPK1 employs a highly dynamic feeding mechanism for RS domain phosphorylation in which the N-terminal portion of RS1 is initially .