Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia.
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.
Tsukada
S
S
Howard Hughes Medical Institute, University of California, Los Angeles 90024.
Saffran
D C
DC
Rawlings
D J
DJ
Parolini
O
O
Allen
R C
RC
Klisak
I
I
Sparkes
R S
RS
Kubagawa
H
H
Mohandas
T
T
Quan
S
S
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
D012333:RNA, Messenger; D004247:DNA; D011505:Protein-Tyrosine Kinases