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Swiprosin 1 – regulator of proximal BCR signaling

The adaptor protein Swiprosin-1/Efhd2 that we identified recently in B cell lipid rafts exhibits its highest expression in immature B cells. Swiprosin-1/Efhd2 consists of a proline rich domain, two EF-hands and a C-terminal coiled-coil domain. Knock-down of Swiprosin-1/Efhd2 in an immature B cell line with a shRNA directed against the 3'-UTR (WEHI231shSw1) impaired spontaneous and BCR-elicited apoptosis. Due to co-clustering of a Swiprosin-1-EGFP fusion protein with the B-cell receptor we expected Swiprosin-1 to be a player in proximal BCR signaling. Indeed, downregulation of Swiprosin-1 attenuated total tyrosine phosphorylation and diminished BCR induced intracellular calcium flux. In contrast, WEHI231 cells ectopically expressing Swiprosin-1 showed increased, but shortened total tyrosine phosphorylation at early time points, as well as increased BCR induced calcium flux. Concomitantly, transient re-expression of Swiprosin-1 in WEHI231shSW1 cells restored BCR-induced calcium flux.

These data suggested interactions of Swiprosin-1 with central elements of the BCR signaling cascade. In fact, GST-pulldown experiments showed that Swiprosin-1 can interact with tyrosine-phosphorylated proteins of ~145 and 70 kDa. With this assay we identified the protein tyrosine kinase Syk in its phosphorylated form as interaction partner of Swiprosin-1. The interaction of pSyk with Swiprosin-1 is mediated by the C-terminal part of Swiprosin-1 because a deletion mutant of Swiprosin-1 lacking the EF-hands and the coiled-coil domain of Swiprosin-1 did not show any interaction with pSyk. We next tested the kinase activity of Syk as a function of Swiprosin-1 levels. Interestingly, immune complex kinase assays showed that BCR-induced Syk activity was reduced in WEHI231shSw1 cells.

Hence, Swiprosin-1 could regulate proximal BCR signaling through maintenance of Syk activity.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kroczek, C., Lang, C., Nitschke, L. et al. Swiprosin 1 – regulator of proximal BCR signaling. Cell Commun Signal 7 (Suppl 1), A79 (2009).

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