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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Agammaglobulinemia / enzymology*
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Agammaglobulinemia / genetics*
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Agammaglobulinemia / immunology
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Amino Acid Sequence
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Animals
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B-Lymphocytes / enzymology*
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Blotting, Northern
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Blotting, Southern
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Cell Line
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Chromosome Mapping
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Cloning, Molecular
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Cosmids
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Cytoplasm / enzymology
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DNA / genetics
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DNA / isolation & purification
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Genetic Carrier Screening
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Humans
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Hybrid Cells / cytology
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Mice
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Molecular Sequence Data
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Protein-Tyrosine Kinases / deficiency*
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Protein-Tyrosine Kinases / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Transcription, Genetic
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Tumor Cells, Cultured
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X Chromosome*
Substances
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RNA, Messenger
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DNA
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Protein-Tyrosine Kinases
Associated data
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GENBANK/L08967
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GENBANK/L20977
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GENBANK/L33702
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GENBANK/L33703
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GENBANK/L33704
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GENBANK/L33705
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GENBANK/L33706
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GENBANK/L33707
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GENBANK/L33708
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GENBANK/L33709