The SH2 Domains of Src Family Kinases Associate with Syk

Abstract

Src family kinases (Lyn, Fyn, Lck, and Blk) and Syk, a tandem SH2 domain containing tyrosine kinase, have been demonstrated to be associated with the antigen receptor in B cells. Both of these categories of tyrosine kinases are presumed to be critical players in the process of antigen-mediated signal transduction. Cross-linking of membrane immunoglobulin on the surface of B cells leads to the activation of Lyn, Fyn, and Blk, which presumably associate with the cytoplasmic tails of the membrane immunoglobulin-associated Ig alpha/beta heterodimer. Receptor ligation also leads to the tyrosine phosphorylation and catalytic activation of Syk, but the mechanism of association of this kinase with the antigen receptor remains to be established. A number of phosphoproteins that can associate with the SH2 domains of Blk, Lyn, and Fyn have been described in activated B cells. We demonstrate here that Syk is one of the proteins in the lysates of activated B cells which bind to the SH2 domains of Src family kinases. Syk binds directly to the SH2 domain of Blk and complexes in vivo with Lyn and Blk in activated B cells.

Ligation of HLA-DR Molecules on B Cells Induces Enhanced Expression of IgM Heavy Chain Genes in Association with Syk Activation

“…5), suggesting a possible suppressive role of Src kinase(s) in Syk activation (49). It was also reported that Src family kinases (Lyn and Btk) co-immunoprecipitate with Syk in activated B cells (50,51). It is thus likely that the agarosebound Syk used in our current study also carries these kinases.…”

Antigen receptor signaling: integration of protein tyrosine kinase functions

“…Since the phosphorylation of these sites in Syk is also required for the activation of Lck, by its phosphorylation at Y192 within its SH2 domain, it is possible that Syk is also involved in the positive regulation of Srcfamily kinases (Couture et al, 1994b). This further suggests that the observed association between Lck and Syk in stimulated cells (Couture et al, 1994b) and the binding of SH2 domains of various members of the Src-family of kinases to tyrosyl phosphorylated Syk in vitro (Aoki et al, 1995;Couture et al, 1994a) is mediated by Syk's phosphorylation at Y518/519. The corresponding tyrosyl residues within the activation loop of ZAP-70 ± Y492 and Y493 have also been shown to undergo phosphorylation following TCR aggregation, and to be essential for the signaling function of ZAP-70 Wange et al, 1995).…”

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

“…BLK is a member of the Src kinase family involved in B-cell receptor signaling, 188 and might be important for the development of the B-cell repertoire. Two recent GWASs revealed BLK to be a novel risk locus for SLE.…”