Synergistic activation of PKD by the B cell antigen receptor and CD19 requires PI3K, Vav1 and PLCγ

Antigens coated with complement fragments coligate the B cell receptor (13CR) with the CD21/CD19 complex which results in synergistic activation of B cells. Previous studies identified PI3K, Vav proteins and PLC-gamma as important components of this synergy. We now show that protein kinase D (also known as PKC mu) is also a point of convergence of these signalling pathways. We found that PKD activation upon BCR engagement or coligation of the BCR with CD19 is entirely dependent on PI3K and PLC-gamma but differ in the requirement for Vav proteins. Whereas PKD activation is Vav1 and Vav2 dependent in response to BCR cross-linking, PKD activation is sensitive to the lack of Vav1 under synergistic stimulation of BCR and CD19. These findings show that Vav proteins and PI3K regulation of PLC-gamma contributes to the activation of PKD in response to BCR and or CD19 cross-linking. (c) 2005 Elsevier Inc. All rights reserved.