Membrane domains and the immunological synapse: keeping T cells resting and ready - PubMed (original) (raw)
Review
Membrane domains and the immunological synapse: keeping T cells resting and ready
Michael L Dustin. J Clin Invest. 2002 Jan.
No abstract available
Figures
Figure 1
Regulation of Lck by rafts and Cbp. Cbp is localized to rafts in resting cells, where it is phosphorylated by active Lck*, an Src family PTK. This modification recruits Csk, which inactivates Lck† by phosphorylating its C-terminal regulatory site, and PEP, which dephosphorylates the Lck activation loop. Another phosphatase, CD45, is localized outside the rafts but may have access to Lck at the lateral boundary or during rare meetings due to partitioning into the same membrane domain. Activation of the TCR results in dephosphorylation of Cbp through the action of an unidentified phosphatase, thus removing the inhibitory complex containing Csk and PEP.
Figure 2
Hypothesis for agrin regulation of immunological synapse formation. (a) Raft-aggregating activity of agrin proteoglycan is regulated by intramolecular interaction with heparan sulfate chains. (b) When these chains are degraded by the lymphocyte heparanase, the raft-aggregating activity is expressed. (c) Recent evidence indicates that T cell agrin glycoprotein (agrinact) enhances synapse formation and T cell activation. Conversely, if agrin glycoprotein is prevented from entering the synapse, perhaps through an interaction with laminin or other ECM components, the formation of the synapse may be destabilized by ectopic raft aggregates, thus preventing T cell activation. Thus, in the presence of specific ECM components, the effect of actin conversion from proteoglycan to glycoprotein may be inhibitory, whereas in an ECM-depleted site like a lymph node it may enhance responses.
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