This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Niklinska, B B Articles by Ashwell, J D Search for Related Content PubMed PubMed Citation Articles by Niklinska, B B Articles by Ashwell, J D

CD45 tyrosine phosphatase activity and membrane anchoring are required for T-cell antigen receptor signaling.

Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.

ABSTRACT

T cells that lack the CD45 transmembrane tyrosine phosphatase have a variety of T-cell receptor (TCR) signaling defects that are corrected by reexpression of wild-type CD45 or its intracytoplasmic domains. In this study, a chimeric molecule containing the myristylation sequence of Src and the intracellular portion of CD45, previously shown to restore function in CD45- T cells, was mutagenized to determine if membrane-associated CD45 tyrosine phosphatase activity is required to restore TCR-mediated signaling in CD45- T cells. Abolition of enzymatic activity by substitution of a serine for a critical cysteine in the first catalytic domain resulted in failure of this molecule to restore TCR signaling. Another mutation, in which a single amino acid substitution destroyed the myristylation site, resulted in failure of the chimeric molecule to partition to the plasma membrane. Although expressed at high levels and enzymatically active, this form of intracellular CD45 also failed to restore normal signaling in CD45- T cells. These findings strongly suggest that CD45's function in TCR signaling requires its proximity to membrane-associated tyrosine phosphatase substrates.

This article has been cited by other articles:

• Davidson, D., Bakinowski, M., Thomas, M. L., Horejsi, V., Veillette, A. (2003). Phosphorylation-Dependent Regulation of T-Cell Activation by PAG/Cbp, a Lipid Raft-Associated Transmembrane Adaptor. Mol. Cell. Biol. 23: 2017-2028 [Abstract] [Full Text]  
• Kashio, N., Matsumoto, W., Parker, S., Rothstein, D. M. (1998). The Second Domain of the CD45 Protein Tyrosine Phosphatase Is Critical for Interleukin-2 Secretion and Substrate Recruitment of TCR-zeta in Vivo. J. Biol. Chem. 273: 33856-33863 [Abstract] [Full Text]  
• Duplay, P., Alcover, A., Fargeas, C., Sekaly, R. P., Branton, P. E. (1996). An Activated Epidermal Growth Factor Receptor/Lck Chimera Restores Early T Cell Receptor-mediated Calcium Response in a CD45-deficient T Cell Line. J. Biol. Chem. 271: 17896-17902 [Abstract] [Full Text]