The src homology domain 2-containing inositol phosphatase SHIP forms a ternary complex with Shc and Grb2 in antigen receptor-stimulated B lymphocytes.
The inositol phosphatase SHIP has been implicated in signaling events downstream of a variety of receptors and is thought to play an inhibitory role in stimulated B cells. We and others have reported that SHIP is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR) cross-linking and forms a complex with the adapter protein Shc. Here, we report that cross-linking of the BCR induces association between Grb2 and SHIP as well as association between Shc and SHIP. We made use of a Grb2-deficient B cell line to demonstrate both in vitro and in vivo that Grb2 expression is required for the efficient association between Shc and SHIP. The results indicate that SHIP, Shc, and Grb2 form a ternary complex in stimulated B cells, with Grb2 stabilizing the interaction between Shc and SHIP. The interactions between Shc, Grb2, and SHIP are therefore analogous to the interactions between Shc, Grb2, and SOS. Shc and Grb2 may help to localize SHIP to the cell membrane, regulating SHIP's inhibitory function following BCR stimulation.
Harmer
S L
SL
G. W. Hooper Foundation and the Departments of Biochemistry and Biophysics and Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
DeFranco
A L
AL
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D051380:GRB2 Adaptor Protein; D008213:Lymphocyte Activation; D051379:Mice; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases