Qualitatively distinct signaling through T cell antigen receptor subunits.
T cell antigen receptors (TCR) contain several subunits including CD3gamma, delta, and epsilon, and TCRzeta and eta which are capable of mediating signal transduction. It is unclear whether the signaling function of these subunits is completely redundant. To assess the relative signaling capabilities of TCR subunits, we compared proximal events in signal transduction by wild-type TCR complexes and TCR devoid of functional zeta subunits, as well as chimeric receptors containing the cytoplasmic domains of TCRzeta or CD3epsilon. Results demonstrate that in BW5147 wild-type TCR, tail-less zeta TCR, CD3epsilon, and TCRzeta transduce signals leading to tyrosine phosphorylation of similar sets of cellular substrates, including the receptor subunits, Fyn, ZAP-70, and phospholipase Cgamma1 (PLCgamma1). Surprisingly, unlike wild-type TCR, tail-less zeta TCR, and CD3epsilon, TCRzeta was incapable of transducing signals resulting in inositol triphosphate (IP3) generation or intracellular free calcium ([Ca2+]i) mobilization. These data indicate that tyrosine phosphorylation of PLCgamma1 is not sufficient to drive IP3 production and [Ca2+]i mobilization. Most importantly, data presented indicate that TCRzeta and CD3epsilon engage partially distinct signaling pathways.
Jensen
W A
WA
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Pleiman
C M
CM
Beaufils
P
P
Wegener
A M
AM
Malissen
B
B
Cambier
J C
JC
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D017252:CD3 Complex / Q000502:physiology; D016827:CD8 Antigens / Q000502:physiology; D002118:Calcium / Q000502:physiology; D004789:Enzyme Activation; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000378:metabolism
D017252:CD3 Complex; D016827:CD8 Antigens; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019000:Phosphotyrosine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium