Lin, Joseph
http://hdl.handle.net/10211.1/1514
2024-03-28T14:23:11Z
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T Cell Receptor Signalling
http://hdl.handle.net/10211.1/1733
T Cell Receptor Signalling
Lin, Joseph; Weiss, Arthur
Published and copyright by Company of Biologists.
2001-01-01T00:00:00Z
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The c-SMAC: Sorting It All Out (or in)
http://hdl.handle.net/10211.1/1517
The c-SMAC: Sorting It All Out (or in)
Lin, Joseph; Miller, Mark J.; Shaw, Andrey S.
T cells integrate and transduce the key signals necessary
to mount an appropriate immune response. To do this,
they rely on both secreted factors as well as physical cell–
cell contact. Much attention has focused on the organization
of proteins at the contact area between a T cell and an
antigen-presenting cell, known as the immunological
synapse. It has been shown in vitro that proteins segregate
into two distinct regions within this contact area, a central
area referred to as the c-SMAC, where the T cell receptor
and associated signaling molecules are enriched, and a
peripheral region called the p-SMAC containing LFA-1
and the scaffolding protein talin. Whether or not these
structures form in vivo and how they function in T cell
activation remain issues of great interest. Here, we review
recently published work and propose several possible
functions for the role of the c-SMAC in T cell activation.
© Lin, Joseph, Mark Miller, and Andrey Shaw. 2005. Originally published in The Journal of Cell Biology. doi: 10.1083/jcb.200503032.
2005-07-18T00:00:00Z
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The Tyrosine Phosphatase CD148 is Excluded from the Immunologic Synapse and Down-regulates Prolonged T Cell Signaling
http://hdl.handle.net/10211.1/1515
The Tyrosine Phosphatase CD148 is Excluded from the Immunologic Synapse and Down-regulates Prolonged T Cell Signaling
Lin, Joseph; Weiss, Arthur
CD148 is a receptor-like protein tyrosine phosphatase
up-regulated on T cells after T cell receptor
(TCR) stimulation. To examine the physiologic role
of CD148 in TCR signaling, we used an inducible CD148-
expressing Jurkat T cell clone. Expression of CD148 inhibits
NFAT (nuclear factor of activated T cells) activation induced
by soluble anti-TCR antibody, but not by antigen-presenting
cells (APCs) loaded with staphylococcal enterotoxin superantigen
(SAg) or immobilized anti-TCR antibody. Immunofluorescence
microscopy revealed that the extracellular
C
domain of CD148 mediates its exclusion from the immunologic
synapse, sequestering it from potential substrates.
Targeting of the CD148 phosphatase domain to the immunologic
synapse potently inhibited NFAT activation by all
means of triggering through the TCR. These data lead us to
propose a model where CD148 function is regulated in
part by exclusion from substrates in the immunologic synapse.
Upon T cell–APC disengagement, CD148 can then
access and dephosphorylate substrates to down-regulate
prolongation of signaling.
© Joseph Lin and Arthur Weis, 2011. Originally published in The Journal of Cell Biology. doi: 10.1083/jcb.200303040.
2003-08-11T00:00:00Z