Publication Date:
2001-09-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffiths, E K -- Krawczyk, C -- Kong, Y Y -- Raab, M -- Hyduk, S J -- Bouchard, D -- Chan, V S -- Kozieradzki, I -- Oliveira-Dos-Santos, A J -- Wakeham, A -- Ohashi, P S -- Cybulsky, M I -- Rudd, C E -- Penninger, J M -- New York, N.Y. -- Science. 2001 Sep 21;293(5538):2260-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11567140" target="_blank"〉PubMed〈/a〉
Keywords:
Actins/metabolism
;
*Adaptor Proteins, Signal Transducing
;
Animals
;
Antigens, CD/metabolism
;
Antigens, CD3/metabolism
;
Antigens, Differentiation, T-Lymphocyte/metabolism
;
B-Lymphocytes/immunology
;
Carrier Proteins/genetics/*physiology
;
Cell Adhesion
;
Cell Adhesion Molecules/metabolism
;
Chimera
;
Gene Targeting
;
Humans
;
Immunization
;
Immunoglobulin G/biosynthesis
;
Integrins/*metabolism
;
Intercellular Adhesion Molecule-1/metabolism
;
Interferon-gamma/biosynthesis
;
Interleukin-2/biosynthesis/pharmacology
;
Lectins, C-Type
;
*Lymphocyte Activation
;
Lymphocyte Function-Associated Antigen-1/metabolism
;
Mice
;
Phosphoproteins/genetics/*physiology
;
Receptors, Antigen, T-Cell/immunology/metabolism
;
Receptors, Interleukin-2/metabolism
;
Recombinant Proteins/metabolism
;
Signal Transduction
;
T-Lymphocytes/immunology/metabolism/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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