Disease relevance of Sfrs5

• Pathogenic determinants in the U3 region of recombinant murine leukemia viruses isolated from CWD and HRS/J mice [1].
• HRS inhibits EGF receptor signaling in the RT4 rat schwannoma cell line [2].

High impact information on Sfrs5

• This alternative splicing was dependent on a purine-rich region within the EIIIB exon to which HRS specifically bound [3].
• HRS/SRp40 expression is elevated in liver cell proliferation during development, regeneration, and oncogenesis [3].
• Furthermore, in an in vivo assay, HRS, and not other SR proteins, directly mediated EIIIB exon inclusion in the fibronectin transcript [3].
• Insulin regulates alternative splicing of PKCbetaII mRNA by phosphorylation of SRp40 via a phosphatidylinositol 3-kinase pathway (Patel, N. A., Chalfant, C. E., Watson, J. E., Wyatt, J. R., Dean, N. M., Eichler, D. C., and Cooper, D. C. (2001) J. Biol. Chem. 276, 22648-22654) [4].
• In the absence of LY294002, overexpression of SRp40 in L6 cells mimicked insulin-induced exon inclusion [5].

Biological context of Sfrs5

• Alternative splicing and structure of the human and mouse SFRS5/HRS/SRp40 genes [6].
• The mouse HRS gene spans 5050 bp and contains eight exons and seven introns [6].
• Mutation of Ser86 on SRp40 blocked in vitro phosphorylation [4].
• Transcriptional up-regulation of the delayed early gene HRS/SRp40 during liver regeneration. Interactions among YY1, GA-binding proteins, and mitogenic signals [7].
• Mutational studies indicated the SRp40 binding site promotes splice site selection [8].

Anatomical context of Sfrs5

• Insulin regulates alternative splicing of protein kinase C beta II through a phosphatidylinositol 3-kinase-dependent pathway involving the nuclear serine/arginine-rich splicing factor, SRp40, in skeletal muscle cells [5].
• By taking advantage of a well known inhibitor of PI 3-kinase, LY294002, we demonstrated that pretreatment of L6 myotubes with LY294002 blocked insulin-induced PKCbetaII exon inclusion as well as phosphorylation of SRp40 [5].
• HRS expression also targeted EGFR to late endosomes [2].
• Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) is required for trafficking of cell surface receptors to the lysosome [2].
• These events involve rapid turnover of the tissues and cells, including disappearance of epithelial cells of HRS [9].

Associations of Sfrs5 with chemical compounds

• When antisense oligonucleotides targeted to a putative SRp40-binding sequence in the betaII-betaI intron were transfected into L6 cells, insulin effects on splicing and glucose uptake were blocked [5].

Analytical, diagnostic and therapeutic context of Sfrs5

• Sequence analysis of HRS, a highly insulin-induced delayed-early gene, demonstrated that it is a member of the family of regulators of alternative pre-mRNA splicing [10].

References