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The Journal of Immunology, 1999, 163: 563-568.
Copyright © 1999 by The American Association of Immunologists

Cas-L Is Required for ß1 Integrin-Mediated Costimulation in Human T Cells1

Kenjiro Kamiguchi*, Kouichi Tachibana*, Satoshi Iwata*, Yoshiyuki Ohashi* and Chikao Morimoto2,*,{dagger}

* Division of Tumor Immunology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115; and {dagger} Department of Clinical Immunology and AIDS Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

ß1 integrins provide a costimulus for TCR/CD3-driven T cell activation and IL-2 production in human peripheral T cells. However, this ß1 integrin-mediated costimulation is impaired in a human T lymphoblastic line, Jurkat. We studied the molecular basis of this impaired costimulation and found that Cas-L, a 105-kDa docking protein, is marginally expressed in Jurkat T cells, whereas Cas-L is well expressed in peripheral T cells. Cas-L is a binding protein and a substrate for focal adhesion kinase and is tyrosine phosphorylated by ß1 integrin stimulation. We here show that the transfection of wild-type Cas-L in Jurkat T cells restores ß1 integrin-mediated costimulation. However, Cas-L transfection had no effect on CD28-mediated costimulation, indicating that Cas-L is specifically involved in the ß1 integrin-mediated signaling pathway. Furthermore, transfection of the Cas-L{Delta}SH3 mutant failed to restore ß1 integrin-mediated costimulation in Jurkat cells. Cas-L{Delta}SH3 mutant lacks the binding site for focal adhesion kinase and is not tyrosine phosphorylated after ß1 integrin stimulation. These findings strongly suggest that the tyrosine phosphorylation of Cas-L plays a key role in the signal transduction in the ß1 integrin-mediated T cell costimulation.




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