The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/6/1863/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 11, June 1, 1998 1863-1870

Articles

Disruption of Lymphocyte Function and Signaling in CD45–associated Protein–null Mice

Akio Matsuda*, Satoshi Motoya*, Shioko Kimura{ddagger}, Renee McInnis*, Abby L. Maizel*, and Akiko Takeda*

From the * Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the {ddagger} Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

CD45-AP specifically associates with CD45, a protein tyrosine phosphatase essential for lymphocyte differentiation and antigen receptor–mediated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src family protein tyrosine kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP–null mice were created to examine the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes showed reduced proliferation in response to antigen receptor stimulation. Both mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were also markedly decreased in CD45-AP–null mice. Interestingly, the interaction between CD45 and Lck was significantly reduced in CD45-AP–null T cells, indicating that CD45-AP directly or indirectly mediates the interaction of CD45 with Lck. Our data indicate that CD45-AP is required for normal antigen receptor signaling and function in lymphocytes.

Key Words: CD45-AP • CD45 • Lck • gene targeting • signal transduction

Address correspondence to Akiko Takeda, Department of Pathology, Roger Williams Hospital-Brown University, 825 Chalkstone Ave., Providence, RI 02908. Phone: 401-456-6557; Fax: 401-456-6569; E-mail: akiko_takeda{at}brown.edu

Satoshi Motoya's present address is First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan 060

Abbreviations used: AP, associated protein; ES, embryonic stem; PKC, protein kinase C; PTK, protein tyrosine kinase; PTP, protein tyrosine phosphatase.


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