The sequence of events in T-cell antigen receptor (TCR) signalling leading to T-cell activation involves regulation of a number of protein tyrosine kinases (PTKs) and the phosphorylation status of many of their substrates. Proximal signalling pathways involve PTKs of the Src, Syk, Csk and Tec families, adapter proteins and effector enzymes in a highly organized tyrosine-phosphorylation cascade. In intact cells, tyrosine phosphorylation is rapidly reversible and generally of a very low stoichiometry even under induced conditions due to the fact that the enzymes removing phosphate from tyrosine-phosphorylated substrates, the protein tyrosine phosphatases (PTPases), have a capacity that is several orders of magnitude higher than that of the PTKs. It follows that a relatively minor change in the PTK/PTPase balance can have a major impact on net tyrosine phosphorylation and thereby on activation and proliferation of T-cells. This review focuses on the involvement of PTKs and PTPases in positive and negative regulation of T-cell activation, the emerging theme of reciprocal regulation of each type of enzyme by the other, as well as regulation of phosphotyrosine turnover by Ser/Thr phosphorylation and regulation of localization of signal components.
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April 2003
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Review Article|
April 01 2003
Positive and negative regulation of T-cell activation through kinases and phosphatases
Tomas MUSTELIN;
Tomas MUSTELIN
∗Program of Signal Transduction, Cancer Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.,
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Kjetil TASKÉN
Kjetil TASKÉN
1
†Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, P.O.B. 1112, Blindern, N-0317 Oslo, Norway
1To whom correspondence should be addressed, at: Department of Medical Biochemistry, University of Oslo, P.O.B. 1112, Blindern, N-0317 Oslo, Norway (e-mail kjetil.tasken@basalmed.uio.no).
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Publisher: Portland Press Ltd
Received:
October 21 2002
Revision Received:
December 12 2002
Accepted:
December 16 2002
Accepted Manuscript online:
December 16 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (1): 15–27.
Article history
Received:
October 21 2002
Revision Received:
December 12 2002
Accepted:
December 16 2002
Accepted Manuscript online:
December 16 2002
Citation
Tomas MUSTELIN, Kjetil TASKÉN; Positive and negative regulation of T-cell activation through kinases and phosphatases. Biochem J 1 April 2003; 371 (1): 15–27. doi: https://doi.org/10.1042/bj20021637
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