Essential role of LAT in T cell development.
The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement. Phosphorylated LAT binds many critical signaling molecules. The central role of this molecule in TCR-mediated signaling has been demonstrated by experiments in a LAT-deficient cell line. To probe the role of LAT in T cell development, the LAT gene was disrupted by targeting. LAT-deficient mice appeared healthy. Flow cytometric analysis revealed normal B cell populations but the absence of any mature peripheral T cells. Intrathymic development was blocked within the CD4- CD8- stage. No gross abnormality of NK or platelet function was observed. LAT is thus critical to both T cell activation and development.
Zhang
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Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sommers
C L
CL
Burshtyn
D N
DN
Stebbins
C C
CC
DeJarnette
J B
JB
Trible
R P
RP
Grinberg
A
A
Tsay
H C
HC
Jacobs
H M
HM
Kessler
C M
CM
Long
E O
EO
Love
P E
PE
Samelson
L E
LE
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta