Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap

EK Griffiths, C Krawczyk, YY Kong, M Raab, SJ Hyduk… - Science, 2001 - science.org
EK Griffiths, C Krawczyk, YY Kong, M Raab, SJ Hyduk, D Bouchard, VS Chan, I Kozieradzki
Science, 2001science.org
The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor
(TCR), but whether it plays a positive or negative role is controversial. We demonstrate that
Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response
to TCR stimulation. Fyb/Slap is also required in vivo for T cell–dependent immune
responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR
signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates …
The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell–dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.
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