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Molecular and Cellular Biology, November 2004, p. 9986-9999, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.9986-9999.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Yeun Ju Kim,1,2 Fujio Sekiya,1 Benoit Poulin,1,{dagger} Yun Soo Bae,2 and Sue Goo Rhee1*

Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland,1 Center for Cell Signaling Research and Division of Molecular Life Sciences, Ewha Womans University, Seoul, South Korea2

Received 24 February 2004/ Returned for modification 2 May 2004/ Accepted 17 August 2004

Phospholipase C-{gamma}2 (PLC-{gamma}2) plays an important role in B-cell signaling. Phosphorylation of various tyrosine residues of PLC-{gamma}2 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-{gamma}2 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-{gamma}2. 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-{gamma}2 molecules.

* Corresponding author. Mailing address: Building 50, Room 3523, 50 South Dr., MSC 8015, Bethesda, MD 20892. Phone: (301) 496-9646. Fax: (301) 480-0357. E-mail: sgrhee{at}nih.gov.

{dagger} Present address: Interactions Cellulaires Neuroendocriniennes, UMR 6544-CNRS-Université de la Méditerranée, 13916 Marseille, France.

Molecular and Cellular Biology, November 2004, p. 9986-9999, Vol. 24, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.22.9986-9999.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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