Vav and Rac activation in B cell antigen receptor endocytosis involves Vav recruitment to the adapter protein LAB.
The signal transduction events supporting B cell antigen receptor (BCR) endocytosis are not well understood. We have identified a pathway supporting BCR internalization that begins with tyrosine phosphorylation of the adapter protein LAB. Phosphorylated LAB recruits a complex of Grb2-dynamin and the guanine nucleotide exchange factor Vav. Vav is required for activation of the small GTPases Rac1 and Rac2. All these proteins contribute to (and dynamin, Vav, and Rac1/2 are required for) BCR endocytosis and presentation of antigen to T cells. This is the first description of a sequential signal transduction pathway from BCR to internalization and antigen presentation.
Malhotra
Shikha
S
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, and Department of Cell Biology, University of Oklahoma, Oklahoma City, Oklahoma 73104.
Kovats
Susan
S
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104.
Zhang
Weiguo
W
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Coggeshall
K Mark
KM
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, and Department of Cell Biology, University of Oklahoma, Oklahoma City, Oklahoma 73104. Electronic address: mark-coggeshall@omrf.ouhsc.edu.
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D034281:Dynamins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein
D033942:Adaptor Proteins, Vesicular Transport; D034281:Dynamins; D051380:GRB2 Adaptor Protein; D009479:Neuropeptides; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C495949:Grb2 protein, mouse; C471359:LAB protein, mouse; C484602:Rac1 protein, mouse