Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145-kDa inositol polyphosphate 5-phosphatase, SHIP.
Stimulation of the B cell Ag receptor (BCR) has been reported to induce tyrosine phosphorylation of a 145-kDa protein and its association with the adapter protein Shc. We have identified this protein as the novel inositol polyphosphate 5-phosphatase (SHIP). Further analysis revealed that both maximal phosphorylation of SHIP and its association with Shc require co-clustering with the Fc receptor for IgG (Fc gamma RII) rather than stimulation of the BCR alone. Since co-clustering of the BCR and Fc gamma RII also down-regulates proliferation induced by Ag receptor stimulation, we hypothesize that tyrosine phosphorylation of SHIP and its association with Shc contribute to negative signaling through effects on inositol and phosphatidylinositol metabolism.
Chacko
G W
GW
Department of Microbiology, Ohio State University, Columbus 43210, USA.
Tridandapani
S
S
Damen
J E
JE
Liu
L
L
Krystal
G
G
Coggeshall
K M
KM
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology*; D000072181:Inositol Polyphosphate 5-Phosphatases; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
D014443:Tyrosine; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases