title: p59(fyn)-mediated phosphorylation regulates the activity of the tissue-specific splicing factor rSLM-1.
abstract: The Sam68-like mammalian protein SLM-1 is a member of the STAR protein family and is related to SAM68 and SLM-2. Here, we demonstrate that rSLM-1 interacts with itself, scaffold-attachment factor B, YT521-B, SAM68, rSLM-2, SRp30c, and hnRNP G. rSLM-1 regulates splice site selection in vivo via a purine-rich enhancer. In contrast to the widely expressed SAM68 and rSLM-2 proteins, rSLM-1 is found primarily in brain and, to a much smaller degree, in testis. In the brain, rSLM-1 and rSLM-2 are predominantly expressed in different neurons. In the hippocampal formation, rSLM-1 is present only in the dentate gyrus, whereas rSLM-2 is found in the pyramidal cells of the CA1, CA3, and CA4 regions. rSLM-1, but not rSLM-2, is phosphorylated by p59(fyn). p59(fyn)-mediated phosphorylation abolishes the ability of rSLM-1 to regulate splice site selection, but has no effect on rSLM-2 activity. This suggests that rSLM-1-positive cells could respond with a change of their splicing pattern to p59(fyn) activation, whereas rSLM-2-positive cells would not be affected. Together, our data indicate that rSLM-1 is a tissue-specific splicing factor whose activity is regulated by tyrosine phosphorylation signals emanating from p59(fyn).
authors.affiliation: Klinikum Kassel, Pathology, Mönchebergstr. 41-43, D-34125 Kassel, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stoss
authors.forename: Tatyana
authors.initials: T
authors.lastname: Novoyatleva
authors.forename: Marieta
authors.initials: M
authors.lastname: Gencheva
authors.forename: Manuela
authors.initials: M
authors.lastname: Olbrich
authors.forename: Natalya
authors.initials: N
authors.lastname: Benderska
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D051076:Proto-Oncogene Proteins c-fyn; D017966:Pyramidal Cells / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D000068103:Serine-Arginine Splicing Factors; D019061:src-Family Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C118777:KHDRBS3 protein, human; C513253:Khdrbs1 protein, mouse; C118776:Khdrbs2 protein, mouse; C495435:Khdrbs2 protein, rat; C495436:Khdrbs3 protein, rat; D036961:Matrix Attachment Region Binding Proteins; D009419:Nerve Tissue Proteins; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; C109132:SAFB protein, human; C490768:Ythdc1 protein, rat; D000068103:Serine-Arginine Splicing Factors; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases