T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation.
Triggering of the antigen-specific T cell receptor-CD3 complex (TCR-CD3) stimulates a rapid phospholipase C-mediated hydrolysis of inositol phospholipids, resulting in the production of second messengers and in T cell activation and proliferation. The role of tyrosine phosphorylation in these events was investigated with a tyrosine protein kinase (TPK) inhibitor, genistein. At doses that inhibited TPK activity and tyrosine phosphorylation of the TCR zeta subunit, but not phospholipase C activity, genistein prevented TCR-CD3-mediated phospholipase C activation, interleukin-2 receptor expression, and T cell proliferation. These findings indicate that tyrosine phosphorylation is an early and critical event that most likely precedes, and is a prerequisite for, inositol phospholipid breakdown during receptor-mediated T cell activation.
Mustelin
T
T
Scripps Clinic and Research Foundation, Immunology Department/IMM3, La Jolla, CA 92037.
Coggeshall
K M
KM
Isakov
N
N
Altman
A
A
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017252:CD3 Complex; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D019833:Genistein; D006801:Humans; D006868:Hydrolysis; D007529:Isoflavones / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007529:Isoflavones; D010743:Phospholipids; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D009955:Ornithine Decarboxylase