BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation.
Tyrosine phosphorylation of adaptor proteins permits the B cell antigen receptor (BCR)-associated protein tyrosine kinases to regulate downstream effector molecules. Here, we report the identification of a novel B cell adaptor for phosphoinositide 3-kinase (PI3K), termed BCAP. Tyrosine phosphorylation of BCAP is mediated by Syk and Btk, thereby providing binding site(s) for the p85 subunit of PI3K. Disruption of the BCAP gene in the DT40 B cell line inhibits BCR-mediated phosphatidylinositol 3,4,5-trisphosphate generation, leading to impaired Akt response. Moreover, recruitment of PI3K to glycolipid-enriched microdomains (GEMs) is significantly attenuated in the absence of BCAP. Hence, these data suggest that BCAP bridges BCR-associated kinases to the PI3K pathway by regulating PI3K localization.
Okada
T
T
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan.
Maeda
A
A
Iwamatsu
A
A
Gotoh
K
K
Kurosaki
T
T
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013379:Substrate Specificity; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D002352:Carrier Proteins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D000072377:Syk Kinase; D014443:Tyrosine; C487977:PIK3AP1 protein, human; C487978:Pik3ap1 protein, mouse; C000625949:BTK protein, human; C000606896:SYK protein, human; C000606897:Syk protein, mouse