title: Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia.
abstract: We describe a novel cytoplasmic tyrosine kinase, termed BPK (B cell progenitor kinase), which is expressed in all stages of the B lineage and in myeloid cells. BPK has classic SH1, SH2, and SH3 domains, but lacks myristylation signals and a regulatory phosphorylation site corresponding to tyrosine 527 of c-src. BPK has a long, basic amino-terminal region upstream of the SH3 domain. BPK was evaluated as a candidate for human X-linked agammaglobulinemia (XLA), an inherited immunodeficiency characterized by a severe deficit of B and plasma cells and profound hypogammaglobulinemia. BPK mapped to within 100 kb of a probe defining the polymorphism most closely linked to XLA at DXS178. Reduction in or the absence of BPK mRNA, protein expression, and kinase activity was observed in XLA pre-B and B cell lines. BPK is likely the XLA gene and functions in pathways critical to B cell expansion.
authors.affiliation: Howard Hughes Medical Institute, University of California, Los Angeles 90024.
authors.forename: S
authors.initials: S
authors.lastname: Tsukada
authors.forename: D C
authors.initials: DC
authors.lastname: Saffran
authors.forename: D J
authors.initials: DJ
authors.lastname: Rawlings
authors.forename: O
authors.initials: O
authors.lastname: Parolini
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: I
authors.initials: I
authors.lastname: Klisak
authors.forename: R S
authors.initials: RS
authors.lastname: Sparkes
authors.forename: H
authors.initials: H
authors.lastname: Kubagawa
authors.forename: T
authors.initials: T
authors.lastname: Mohandas
authors.forename: S
authors.initials: S
authors.lastname: Quan
mesh_terms: D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003360:Cosmids; D003593:Cytoplasm / Q000201:enzymology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D006580:Genetic Carrier Screening; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014960:X Chromosome
chemical_list: D012333:RNA, Messenger; D004247:DNA; D011505:Protein-Tyrosine Kinases