p59(fyn)-mediated phosphorylation regulates the activity of the tissue-specific splicing factor rSLM-1

Mol Cell Neurosci. 2004 Sep;27(1):8-21. doi: 10.1016/j.mcn.2004.04.011.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Brain / metabolism*
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Enhancer Elements, Genetic / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Hippocampus / metabolism
  • Matrix Attachment Region Binding Proteins / metabolism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Matrix-Associated Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organ Specificity / genetics
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fyn
  • Pyramidal Cells / metabolism
  • RNA Splice Sites / genetics
  • RNA Splicing / genetics*
  • RNA Splicing Factors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / isolation & purification
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Receptors, Estrogen / metabolism
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Serine-Arginine Splicing Factors
  • src-Family Kinases / genetics
  • src-Family Kinases / isolation & purification
  • src-Family Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Complementary
  • Heterogeneous-Nuclear Ribonucleoproteins
  • KHDRBS3 protein, human
  • Khdrbs1 protein, mouse
  • Khdrbs2 protein, mouse
  • Khdrbs2 protein, rat
  • Khdrbs3 protein, rat
  • Matrix Attachment Region Binding Proteins
  • Nerve Tissue Proteins
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • RNA Splice Sites
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Receptors, Estrogen
  • SAFB protein, human
  • Ythdc1 protein, rat
  • Serine-Arginine Splicing Factors
  • Fyn protein, rat
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases

Associated data

  • GENBANK/AF305618
  • GENBANK/AF305619