Editors' ChoiceImmunology

BCAP Bridges the BCR and PI3K

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Science's STKE  09 Jan 2001:
Vol. 2001, Issue 64, pp. tw10
DOI: 10.1126/stke.2001.64.tw10

The B cell receptor (BCR) activates several signaling pathways including the phosphatidylinositol 3-kinase (PI3K) pathway. Although the B cell protein CD19 can mediate some BCR-dependent activation of PI3K, other proteins also contribute to PI3K activation. Okada et al. have cloned and characterized BCAP (B cell adaptor for PI3K) as a protein that mediates much of PI3K activation in B cells. BCAP is expressed in spleen cells, and in B cell and mast cell lines. BCAP was present as four different molecular sizes that resulted from alternative splicing, and BCAP shares some weak sequence similarity with the Drosophila protein adaptor protein Dof. BCAP appeared to be phosphorylated first by the kinase Syk and then by another kinase, Btk, as demonstrated in several kinase-deficient cell lines. The tyrosine kinase Lyn, however, appeared to attenuate the phosphorylation of BCAP, possibly by interfering with or regulating the kinase activities of Syk and Btk. The p85 subunit of PI3K exhibited inducible association with BCAP that correlated with the phosphorylation of specific BCAP tyrosine moieties. Activation of Akt, a protein kinase substrate of PI3K, was decreased, but not abolished, in BCAP-deficient cells, suggesting that CD19 or another signaling protein was responsible for residual PI3K activation. (JNK) Jun NH2-terminal kinase activation, however, was almost completely blocked. Additionally, BCAP-deficient cells were defective in translocation of PI3K glycolipid rafts. The results suggest that, by acting as a substrate for tyrosine kinases, BCAP contributes to BCR-induced activation of PI3K.

Okada, T., Maeda, A., Iwamatsu, A., Gotoh, K., and Kurosaki, T. (2000) BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation. Immunity 13: 817-827. [Online Journal]

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