Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap.
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.
Griffiths
E K
EK
Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.
Krawczyk
C
C
Kong
Y Y
YY
Raab
M
M
Hyduk
S J
SJ
Bouchard
D
D
Chan
V S
VS
Kozieradzki
I
I
Oliveira-Dos-Santos
A J
AJ
Wakeham
A
A
Ohashi
P S
PS
Cybulsky
M I
MI
Rudd
C E
CE
Penninger
J M
JM
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002678:Chimera; D018390:Gene Targeting; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000099192:CD69 Antigens
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D000099192:CD69 Antigens; C106957:FYB1 protein, human; C491468:Fyb protein, mouse; C065289:ICAM2 protein, human