Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia

S Tsukada, DC Saffran, DJ Rawlings, O Parolini… - Cell, 1993 - cell.com
S Tsukada, DC Saffran, DJ Rawlings, O Parolini, RC Allen, I Klisak, RS Sparkes…
Cell, 1993cell.com
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 …
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.
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