BCAP: The tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation

Okada, T Maeda, A Iwamatsu, A Gotoh, K Kurosaki, T

T. Okada et al., BCAP: The tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation, IMMUNITY, 13(6), 2000, pp. 817-827

50

INGLESE

Article

Immunology

IMMUNITY

1074-7613 → ACNP

13

6

2000

817 - 827

ISI

1074-7613(200012)13:6<817:BTTKST>2.0.ZU;2-4

Tyrosine phosphorylation of adaptor proteins permits the B cell antigen rec eptor (BCR)-associated protein tyrosine kinases to regulate downstream effe ctor molecules. Here, we report the identification of a novel B cell adapto r for phosphoinositide 3-kinase (P13K), termed BCAP. Tyrosine phosphorylati on of BCAP is mediated by Syk and Btk, thereby providing binding site(s) fo r the p85 subunit of P13K. Disruption of the BCAP gene in the DT40 B cell l ine inhibits BCR-mediated phosphatidylinositol 3,4,5-trisphosphate generati on, leading to impaired Akt response. Moreover, recruitment of P13K to glyc olipid-enriched microdomains (GEMs) is significantly attenuated in the abse nce of BCAP. Hence, these data suggest that BCAP bridges BCR-associated kin ases to the P13K pathway by regulating P13K localization.