Temporally regulated assembly of a dynamic signaling complex associated with the activated TCR.
TCR triggering promotes multiple tyrosine kinase-dependent interactions involving proteins with one or more protein binding modules. Reported interactions mostly exceed the binding potential of these proteins. A solution to this paradox is the temporally regulated recruitment of alternative ligands. We have tested this hypothesis by analyzing the time course of protein/protein interactions triggered by TCR engagement. We show that a short-lived and dynamic multimolecular complex is assembled on tyrosine-phosphorylated CD3zeta. Specific components of this complex are recruited and shed in a temporal sequence distinct for each of the proteins analyzed. The temporally regulated assembly of a higher order structure at the activated TCR is likely to be crucial in achieving both signal longevity and signal specificity.
Pacini
S
S
Department of Evolutionary Biology, University of Siena, Italy.
Valensin
S
S
Telford
J L
JL
Ladbury
J
J
Baldari
C T
CT
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D055765:Shc Signaling Adaptor Proteins; C054979:antigen T cell receptor, zeta chain; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase