title: Cloning and characterization of human Src-like adaptor protein 2 and a novel splice isoform, SLAP-2-v.
abstract: Src-like adaptor protein 2 (SLAP-2) is a recently characterized adaptor protein bearing sequence and structural similarity to the Src-like adaptor protein (SLAP). SLAP-2 expression is hematopoietic-specific, and it has been demonstrated to function as a negative regulator of T-cell antigen receptor (TCR)-mediated signalling by virtue of its interaction with c-Cbl. Here we report the cloning of a cDNA encoding the human homologue of SLAP-2, as well as the genomic structure of the human SLAP-2 gene. Similar to its murine counterpart, two human SLAP-2 protein isoforms exist because of alternative translation initiation, and SLAP-2 protein expression is observed in a variety of hematopoietic cell lines of both lymphoid and myeloid lineages. The human SLAP-2 gene is located on chromosome 20q, and the SLAP-2 coding region consists of seven exons. Concurrent with the cloning of the full-length SLAP-2 cDNA, a unique cDNA encoding an alternatively spliced SLAP-2 isoform has been identified, and designated as SLAP-2-v. The SLAP-2-v transcript encodes a putative protein of 210 amino acids that lacks the c-Cbl interaction region, and consequently is impaired in its ability to both bind to c-Cbl, and inhibit TCR signalling relative to SLAP-2.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Loreto
authors.forename: C Jane
authors.initials: CJ
authors.lastname: McGlade
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002890:Chromosomes, Human, Pair 20; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D005091:Exons; D006413:Hematopoietic System / Q000166:cytology / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics* / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; C441328:SLA2 protein, human; D014157:Transcription Factors; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D016392:Proto-Oncogene Proteins pp60(c-src); C067419:CBL protein, human