Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145-kDa inositol polyphosphate 5-phosphatase, SHIP

• Published in: The Journal of immunology (1950) Vol. 157; no. 6; pp. 2234 - 2238
• Main Authors: Chacko, GW, Tridandapani, S, Damen, JE, Liu, L, Krystal, G, Coggeshall, KM
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.1996
• Subjects: Animals; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; Cell Line; Down-Regulation - immunology; Inositol Polyphosphate 5-Phosphatases; Lymphocyte Activation - drug effects; Mice; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation - drug effects; Signal Transduction - drug effects; Signal Transduction - immunology; src Homology Domains; Tyrosine - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.157.6.2234

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.