Mechanism of B-Cell Receptor-Induced Phosphorylation and Activation of Phospholipase C- 2

Ewha Womans University, Sŏul, Seoul, South Korea
Molecular and Cellular Biology (Impact Factor: 4.78). 12/2004; 24(22):9986-99. DOI: 10.1128/MCB.24.22.9986-9999.2004
Source: PubMed


Phospholipase C-γ2 (PLC-γ2) plays an important role in B-cell signaling. Phosphorylation of various tyrosine residues of PLC-γ2
has been implicated in regulation of its lipase activity. With the use of antibodies specific for each of the putative phosphorylation
sites, we have now shown that PLC-γ2 is phosphorylated on Y753, Y759, and Y1217 in response to engagement of the B-cell receptor
in Ramos cells, as well as in murine splenic B cells. In cells stimulated maximally via this receptor, the extent of phosphorylation
of Y1217 was three times that of Y753 or of Y759. Stimulation of Jurkat T cells or platelets via their immunoreceptors also
elicited phosphorylation of Y753 and Y759 but not that of Y1217. A basal level of phosphorylation of Y753 was apparent in
unstimulated lymphocytes. The extent of phosphorylation of Y753 and Y759, but not that of Y1217, correlated with the lipase
activity of PLC-γ2. Examination of the effects of various pharmacological inhibitors and of RNA interference in Ramos cells
suggested that Btk is largely, but not completely, responsible for phosphorylation of Y753 and Y759, whereas phosphorylation
of Y1217 is independent of Btk. Finally, phosphorylation of Y1217 and that of Y753 and Y759 occurred on different PLC-γ2 molecules.

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