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Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb/Slap

Science  21 Sep 2001:
Vol. 293, Issue 5538, pp. 2260-2263
DOI: 10.1126/science.1063397

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Abstract

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.

  • * To whom correspondence should be addressed. E-mail: jpenning{at}amgen.com

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