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.
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, and Department of Cell Biology, University of Oklahoma, Oklahoma City, Oklahoma 73104.
Shikha
S
Malhotra
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104.
Susan
S
Kovats
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Weiguo
W
Zhang
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.
K Mark
KM
Coggeshall
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