A Role for the Tec Family Tyrosine Kinase Txk in T Cell Activation and Thymocyte Selection

doi:10.1084/jem.190.10.1427

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© The Rockefeller University Press, 0022-1007/1999/11/1427/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 10, November 15, 1999 1427-1438

Original Article

A Role for the Tec Family Tyrosine Kinase Txk in T Cell Activation and Thymocyte Selection

Connie L. Sommers^a, Ronald L. Rabin^b, Alexander Grinberg^a, Henry C. Tsay^a, Joshua Farber^b, and Paul E. Love^a
^a Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development,
^b Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Correspondence to: Connie L. Sommers, Bldg. 6B, Rm. 2B-210, 6 Center Dr., MSC 2780, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-2780. Tel:301-496-2291 Fax:301-480-6302 E-mail:connies{at}helix.nih.gov.

Recent data indicate that several members of the Tec familyof protein tyrosine kinases function in antigen receptor signaltransduction. Txk, a Tec family protein tyrosine kinase, isexpressed in both immature and mature T cells and in mast cells.By overexpressing Txk in T cells throughout development, wefound that Txk specifically augments the phospholipase C (PLC)- ${gamma}$ 1–mediatedcalcium signal transduction pathway upon T cell antigen receptor(TCR) engagement. Although Txk is structurally different frominducible T cell kinase (Itk), another Tec family member expressedin T cells, expression of the Txk transgene could partiallyrescue defects in positive selection and signaling in itk^-^/^-mice. Conversely, in the itk^+/+ (wild-type) background, overexpressionof Txk inhibited positive selection of TCR transgenic thymocytes,presumably due to induction of cell death. These results identifya role for Txk in TCR signal transduction, T cell development,and selection and suggest that the Tec family kinases Itk andTxk perform analogous functions.

Key Words: transgenic mice, signal transduction, T cell receptors, phospholipaseC, T cells

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