B cell antigen receptor cross-linking induces tyrosine phosphorylation and membrane translocation of a multimeric Shc complex that is augmented by CD19 co-ligation.
The SH2 domain-containing transforming Shc protein has been implicated in mitogenic signaling via several surface receptors through p21ras. Following tyrosine phosphorylation by either receptor or non-receptor tyrosine kinases, Shc may interact with the adaptor protein Grb2, which is linked to Sos1, a guanine nucleotide exchange factor for human ras. Ligation of the antigen receptor complex on B cells (BCR) is known to activate various intracellular signaling pathways, which may accumulate in mitogenic responses. With respect to the initial steps, the activation of BCR-associated non-receptor tyrosine kinases appears to be indispensible. In this report we show that Shc proteins become tyrosine phosphorylated after BCR ligation on both transformed and normal human B cells. This is accompanied by the association of Shc with Grb2 proteins and a yet unidentified 145-kDa tyrosine phosphorylated protein. Subcellular fractionation revealed that this activation-induced multimeric Shc complex rapidly translocates towards the plasma membrane. Co-ligation of the BCR with the CD19 molecule results in a marked increase of these events, whereas CD19 cross-linking alone does not induce Shc tyrosine phosphorylation or translocation. Thus, in B cells the Shc complex may represent a molecular junction between the BCR and the mitogenic p21ras cascade.
Lankester
A C
AC
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
van Schijndel
G M
GM
Rood
P M
PM
Verhoeven
A J
AJ
van Lier
R A
RA
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD / Q000502:physiology*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001692:Biological Transport; D015704:CD4 Antigens / Q000502:physiology; D005656:Fungal Proteins / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D006801:Humans; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D020837:SOS1 Protein; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D015704:CD4 Antigens; D005656:Fungal Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins; C528024:SHC1 protein, human; D020837:SOS1 Protein; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)