title: Salpalpha and Salpbeta, growth-arresting homologs of Sam68.
abstract: Sam68, a nuclear RNA-binding protein, is a major substrate of the Src tyrosine kinase in mitotic cells. In addition to a tyrosine-rich C-terminal region, Sam68 also has six poly-proline (SH3-binding) sites, many of which are located in an amino-terminal region. Sam68 appears to act as an adaptor protein, associating with many SH2- and SH3-containing signal-transducing proteins (Richard et al., Mol. Cell. Biol. 15:186-197, 1995). Here we describe a novel 55kDa protein, Salpalpha, which has sequence similarity to Sam68 throughout its length. Salpalpha lacks the amino-terminal region found in Sam68, and has only a single poly-proline site, which binds the SH3 domain of the p85 subunit of PI 3-kinase. Salpalpha is tyrosine-phosphorylated when expressed in Rous sarcoma virus-infected chicken embryo fibroblasts (RSV-CEF); unlike Sam68, however, Salpalpha does not co-precipitate with v-Src. Salpbeta, an alternatively spliced isoform lacking the C-terminal tyrosine-rich region, is also tyrosine-phosphorylated in RSV-CEF, and also binds the SH3 domain of p85. We further show that expression of either Salpalpha or Salpbeta down-regulates the expression of Sam68 in CEF, and arrests the growth of these cells. Our results suggest that Salp may function as a negative regulator of cell growth.
authors.affiliation: University of Texas at Dallas, Department of Molecular Biology, Richardson, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: J G
authors.initials: JG
authors.lastname: Burr
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D002455:Cell Division / Q000235:genetics*; D002642:Chick Embryo; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; C118777:KHDRBS3 protein, human; C513253:Khdrbs1 protein, mouse; C486528:Khdrbs3 protein, mouse; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D015688:Oncogene Protein pp60(v-src)