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Negative regulation of lymphocyte activation by the adaptor protein LAX. J Immunol 2005 May 01;174(9):5612-9

Date

04/22/2005

Pubmed ID

15843560

DOI

10.4049/jimmunol.174.9.5612

Scopus ID

2-s2.0-17844394466   38 Citations

Abstract

The membrane-associated adaptor protein LAX is a linker for activation of T cells (LAT)-like molecule that is expressed in lymphoid tissues. Upon stimulation of T or B cells, it is phosphorylated and interacts with Grb2 and the p85 subunit of PI3K. LAX, however, is not capable of replacing LAT in the TCR signaling pathway. In this study we report that upon T or B cell activation, the LAX protein was up-regulated dramatically. Although disruption of the LAX gene by homologous recombination had no major impact on lymphocyte development, it caused a significant reduction in CD23 expression on mature B cells. Interestingly, naive LAX(-/-) mice had spontaneous germinal center formation. Compared with normal T and B cells, LAX(-/-) T and B cells were hyperresponsive and had enhanced calcium flux, protein tyrosine phosphorylation, MAPK and Akt activation, and cell survival upon engagement of the T or B AgRs. Our data demonstrate that LAX functions as a negative regulator in lymphocyte signaling.

Author List

Zhu M, Granillo O, Wen R, Yang K, Dai X, Wang D, Zhang W

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Vesicular Transport
Animals
B-Lymphocytes
Cell Differentiation
Down-Regulation
Gene Targeting
Humans
Jurkat Cells
Lymphocyte Activation
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Antigen, B-Cell
Receptors, Antigen, T-Cell
Signal Transduction
T-Lymphocytes
Up-Regulation
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc