title: Human and mouse DOCK10 splicing isoforms with alternative first coding exon usage are differentially expressed in T and B lymphocytes.
abstract: DOCK10 is a member of the dedicator of cytokinesis (DOCK) family of Rho GTPase activators preferentially expressed in lymphocytes. In this paper, we analyzed DOCK10 mRNA diversity produced because of alternative splicing. Alternative first coding exon usage led to 2 main protein-coding transcripts, DOCK10.1 and DOCK10.2. Full-length cDNA clones of both isoforms were obtained from both normal human peripheral blood mononuclear cells and mouse spleen for the first time for human DOCK10.1, mouse DOCK10.1, and mouse DOCK10.2. Human and mouse DOCK10.1 clones corresponded to the protein coding assemblies provided by the National Center for Biotechnology Information as Reference Sequences for DOCK10. Our analysis especially focused on human cDNA clones, of which 63% were alternatively spliced forms involving diverse exons and introns. DOCK10.1 expression was enriched in normal T cells, and DOCK10.2 expression was enriched in normal B cells and chronic lymphocytic leukemia (CLL) B cells. Both isoforms were upregulated in response to interleukin-4 in B cells, both normal and CLL, but not in T cells. Our data suggest that cell-specific mechanisms regulate expression of the alternative first exon variants of DOCK10 in vertebrates.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Alcaraz-García
authors.forename: Natalia
authors.initials: N
authors.lastname: Ruiz-Lafuente
authors.forename: Silvia
authors.initials: S
authors.lastname: Sebastián-Ruiz
authors.forename: María Juliana
authors.initials: MJ
authors.lastname: Majado
authors.forename: Consuelo
authors.initials: C
authors.lastname: González-García
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Bernardo
authors.forename: María Rocío
authors.initials: MR
authors.lastname: Alvarez-López
authors.forename: Antonio
authors.initials: A
authors.lastname: Parrado
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D019169:Jurkat Cells; D020014:K562 Cells; D051379:Mice; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D007155:Immunologic Factors; D015847:Interleukin-4; D020033:Protein Isoforms; C561785:DOCK10 protein, mouse; C530992:DOCK10 protein, human