CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line.
The human T-cell line Jurkat was found to contain at least two immunologically distinct isoforms of inositol phospholipid-specific phospholipase C (PLC), PLC-beta 1 and PLC-gamma 1. Treatment of Jurkat cells with antibody to CD3 led to phosphorylation of PLC-gamma 1 but not of PLC-beta 1. The phosphorylation of PLC-gamma 1 occurred rapidly and transiently on both serine and tyrosine residues; tyrosine phosphorylation reached a maximum level less than 1 min after stimulation and decreased rapidly, both in the presence and in the absence of orthovanadate. Two-dimensional phosphopeptide map analysis revealed that the major sites of tyrosine and serine phosphorylation in PLC-gamma 1 from activated Jurkat cells are the same as those in PLC-gamma 1 from cells treated with peptide growth factors such as epidermal growth factor and platelet-derived growth factor. Previously, it has been shown that multiple phosphorylation of PLC-gamma 1 by the growth factor receptor tyrosine kinases leads to activation of PLC-gamma 1. Thus, the current data suggest that inositol phospholipid hydrolysis triggered by the T-cell antigen receptor-CD3 complex is due, at least in part, to activation of PLC-gamma 1 and that the mechanism by which this activation is achieved involves phosphorylation of multiple tyrosine residues on PLC-gamma 1 by a nonreceptor tyrosine kinase coupled to the T-cell antigen receptor-CD3 complex.
Park
D J
DJ
Section on Signal Transduction, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Rho
H W
HW
Rhee
S G
SG
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015153:Blotting, Western; D017252:CD3 Complex; D002460:Cell Line; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D010449:Peptide Mapping; D010766:Phosphorylation; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012694:Serine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014357:Trypsin; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D012694:Serine; D010738:Type C Phospholipases; D014357:Trypsin