Adaptable molecular interactions guide phosphorylation of the SR protein ASF/SF2 by SRPK1. 2008

Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA.

The SR (arginine-serine rich) protein ASF/SF2 (also called human alternative splicing factor), an essential splicing factor, contains two functional modules consisting of tandem RNA recognition motifs (RRMs; RRM1-RRM2) and a C-terminal arginine-serine repeat region (RS domain, a domain rich in arginine-serine repeats). The SR-specific protein kinase (SRPK) 1 phosphorylates the RS domain at multiple serines using a directional (C-terminal-to-N-terminal) and processive mechanism--a process that directs the SR protein to the nucleus and influences protein-protein interactions associated with splicing function. To investigate how SRPK1 accomplishes this feat, the enzyme-substrate complex was analyzed using single-turnover and multiturnover kinetic methods. Deletion studies revealed that while recognition of the RS domain by a docking groove on SRPK1 is sufficient to initiate the processive and directional mechanism, continued processive phosphorylation in the presence of building repulsive charge relies on the fine-tuning of contacts with the RRM1-RRM2 module. An electropositive pocket in SRPK1 that stabilizes newly phosphorylated serines enhanced processive phosphorylation of later serines. These data indicate that SRPK1 uses stable, yet highly flexible protein-protein interactions to facilitate both early and late phases of the processive phosphorylation of SR proteins.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068103 Serine-Arginine Splicing Factors A family of regulatory factors essential for constitutive and alternative splicing in RNA metabolism. SR-Rich Splicing Proteins,Serine-Arginine-Rich Splicing Proteins,Factors, Serine-Arginine Splicing,Proteins, SR-Rich Splicing,Proteins, Serine-Arginine-Rich Splicing,SR Rich Splicing Proteins,Serine Arginine Rich Splicing Proteins,Serine Arginine Splicing Factors,Splicing Factors, Serine-Arginine,Splicing Proteins, SR-Rich,Splicing Proteins, Serine-Arginine-Rich
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein

Related Publications

Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
March 2008, Molecular cell,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
October 2010, Journal of molecular biology,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
February 2009, Genes & development,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
March 2000, Nucleic acids research,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
August 2005, Cell,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
August 2009, Acta biochimica et biophysica Sinica,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
April 1999, The Journal of biological chemistry,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
February 1997, Genes & development,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
August 1998, Biochemical and biophysical research communications,
Jonathan C Hagopian, and Chen-Ting Ma, and Bryan R Meade, and Claudio P Albuquerque, and Jacky Chi Ki Ngo, and Gourisankar Ghosh, and Patricia A Jennings, and Xiang-Dong Fu, and Joseph A Adams
October 2005, Molecular cell,
Copied contents to your clipboard!