Cutting edge: association of phospholipase C-gamma 2 Src homology 2 domains with BLNK is critical for B cell antigen receptor signaling.
To explore the mechanism(s) by which phospholipase C (PLC)-gamma 2 participates in B cell Ag receptor (BCR) signaling, we have studied the function of PLC-gamma 2 mutants in B cells deficient in PLC-gamma 2. Mutation of the N-terminal Src homology 2 domain [SH2(N)] resulted in the complete loss of inositol 1,4, 5-trisphosphate generation upon BCR engagement. A possible explanation for the SH2(N) requirement was provided by findings that this mutation abrogates the association of PLC-gamma 2 with an adaptor protein BLNK. Moreover, expression of a membrane-associated form (CD16/PLC-gamma 2) with SH2(N) mutation required coligation of BCR and CD16 for inositol 1,4,5-trisphosphate generation. Together, our results suggest a central role for the SH2(N) domain in directing PLC-gamma 2 into the close proximity of BCR signaling complex by its association with BLNK, whereby PLC-gamma 2 becomes tyrosine phosphorylated and thereby activated.
Ishiai
M
M
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan.
Sugawara
H
H
Kurosaki
M
M
Kurosaki
T
T
D048868:Adaptor Proteins, Signal Transducing; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017452:Receptors, IgG / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D051966:Phospholipase C gamma