Disease relevance of Blk

• Our findings in the lymphoma model show that an initial Ag encounter renders receptors unresponsive to subsequent Ag challenge, as measured by their inability to mobilize Ca2+ and to mediate phosphorylation of receptor-proximal kinases, including Lyn, Blk, and Syk [1].

High impact information on Blk

• This complementary DNA, termed blk (for B lymphoid kinase), specifies a polypeptide of 55 kilodaltons that is related to, but distinct from, previously identified retroviral or cellular tyrosine kinases [2].
• Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR [3].
• B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7 [3].
• Taken together, these results indicate that specific B and T cell progenitor subsets are preferentially susceptible to transformation by Blk(Y495F) and suggest a role for Blk in the control of proliferation during B cell development [4].
• Expression of constitutively active Blk in the T lineage resulted in the appearance of clonal, thymic lymphomas composed of intermediate single positive cells [4].

Biological context of Blk

• Genetic mapping of the gene for a novel tyrosine kinase, Blk, to mouse chromosome 14 [5].
• Blk maps to the proximal region of chromosome 14 with the gene order centromere--(Np-1,Tcra)-Blk-sys-Es-10 [5].
• Tyrosine phosphorylation of Blk and Fyn Src homology 2 domain-binding proteins occurs in response to antigen-receptor ligation in B cells and constitutively in pre-B cells [6].
• Thus, Bcmd may be a direct mutation in Blk, or in a gene involved in Blk regulation, such that excess expression pushes the A/WySnJ transitional B cells past the apoptosis checkpoint to cell death [7].
• Expression of Blk(Y495F) in the B lineage at levels similar to that of endogenous Blk induced B lymphoid tumors of limited clonality, whose phenotypes are characteristic of B cell progenitors at the proB/preB-I to preB-II transition [4].

Anatomical context of Blk

• Immunolocalization of p55blk in normal mouse spleen supports these observations: staining is restricted to lymphocytes and is concentrated in regions rich in B-cells; plasma cells and stromal cells are not stained with anti-Blk antibodies [8].
• Furthermore, transient transfections in HeLa cells proposed that EBF and B cell-specific activator protein were able to cooperate in the activation of a Blk promoter-controlled reporter construct [9].
• Examination of the nucleotide sequence of the B lymphoid kinase (Blk) promoter suggested the presence of an EBF binding site, and in vivo footprinting analysis showed that the site was protected from methylation in a pre-B cell line [9].

Associations of Blk with chemical compounds

• The Blk SH2 domain bound more than 10 distinct phosphoprotein species, most of which reacted with an antiphosphotyrosine antibody; the phosphotyrosine content of these proteins was increased if surface immunoglobulin was cross-linked before extracts were made [10].

Physical interactions of Blk

• The Lyn SH2 binding profile resembled that of Blk, but differences in the binding specificities of these kinases were also observed [10].

Regulatory relationships of Blk

• EMSA indicated that recombinant and cellular EBF interact physically with this site; furthermore, transient transfections indicated that ectopic expression of EBF in nonlymphoid HeLa cells activate a Blk promoter-controlled reporter construct 9-fold [9].

Other interactions of Blk

• A number of Blk and Fyn Src homology 2 domain-binding phosphoproteins were also observed in pre-B cells that had not been stimulated in vitro [6].
• Mutants lacking both tyrosine residues of the immune receptor tyrosine-based activation motif (ITAM) of FcgammaRIIa/c were not phosphorylated by Blk and Fyn, while Lyn-mediated phosphorylation was dependent on the presence of the C-terminal tyrosine of the ITAM [11].
• Several members of the Src family, including Blk, Lyn, Fyn(T), and Lck, are expressed in B cells [10].
• Proteins of 90 kDa, 130 kDa, and 150 kDa were preferentially bound by the Blk SH2 domain, while the Fyn(T) SH2 domain showed preferential binding to proteins of 76 and 180 kDa [10].

Analytical, diagnostic and therapeutic context of Blk

• The gene Blk, which encodes a novel tyrosine kinase expressed preferentially in B-lymphoid cells, was mapped by Southern blot analysis of DNA from the progeny of an intersubspecific backcross [5].
• Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk [12].
• The Blk genomic structure was highly homologous to BIK: Sequence analysis ruled out coding region mutations, but Blk transcripts were overly abundant in sorted A/WySnJ T1 B cells [7].

References