CD19 as a membrane-anchored adaptor protein of B lymphocytes: costimulation of lipid and protein kinases by recruitment of Vav.
CD19 is a coreceptor that amplifies signaling by membrane immunoglobulin (mIg) to promote responses of the B lymphocyte to T-dependent antigens. Vav is a guanine nucleotide exchange factor for the Rho, Rac, Cdc42 family of small GTPases. We found that coligating mIg and CD19 causes a synergistic increase in the tyrosine phosphorylation of CD19. Phosphorylated tyrosine-391 of CD19 binds Vav to mediate a sustained increase in intracellular Ca2+ concentration. This response correlates with activation by the CD19-Vav complex of phosphatidylinositol 4-phosphate 5-kinase for the synthesis of phosphatidylinositol 4,5-bisphosphate. Interaction of CD19 with Vav also mediates the synergistic activation of the mitogen-activated protein kinase JNK. Therefore, CD19 is a membrane adaptor protein that recruits Vav for the activation of lipid and protein kinases.
O'Rourke
L M
LM
Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom.
Tooze
R
R
Turner
M
M
Sandoval
D M
DM
Carter
R H
RH
Tybulewicz
V L
VL
Fearon
D T
DT
D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004789:Enzyme Activation; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
D018941:Antigens, CD19; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; C496620:Vav1 protein, rat; D014443:Tyrosine; D011494:Protein Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium