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Originally published In Press as doi:10.1074/jbc.M703157200 on May 16, 2007

J. Biol. Chem., Vol. 282, Issue 29, 20925-20932, July 20, 2007
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Differential Function of PTP{alpha} and PTP{alpha} Y789F in T Cells and Regulation of PTP{alpha} Phosphorylation at Tyr-789 by CD45*

Lola Maksumova{ddagger}1, Yanni Wang§, Nelson K. Y. Wong§, Hoa T. Le2, Catherine J. Pallen{ddagger}3, and Pauline Johnson§4

From the Departments of {ddagger}Pediatrics, §Microbiology and Immunology, and Pathology and Laboratory Medicine, University of British Columbia and Child & Family Research Institute, Vancouver, British Columbia V6T 1Z3, Canada

CD45 is a major membrane protein tyrosine phosphatase (PTP) expressed in T cells where it regulates the activity of Lck, a Src family kinase important for T cell receptor-mediated activation. PTP{alpha} is a more widely expressed transmembrane PTP that has been shown to regulate the Src family kinases, Src and Fyn, and is also present in T cells. Here, PTP{alpha} was phosphorylated at Tyr-789 in CD45 T cells but not in CD45+ T cells suggesting that CD45 could regulate the phosphorylation of PTP{alpha} at this site. Furthermore, CD45 could directly dephosphorylate PTP{alpha} in vitro. Expression of PTP{alpha} and PTP{alpha}-Y789F in T cells revealed that the mutant had a reduced ability to decrease Fyn and Cbp phosphorylation, to regulate the kinase activity of Fyn, and to restore T cell receptor-induced signaling events when compared with PTP{alpha}. Conversely, this mutant had an increased ability to prevent Pyk2 phosphorylation and CD44-mediated cell spreading when compared with PTP{alpha}. These data demonstrate distinct activities of PTP{alpha} and PTP{alpha}-Y789F in T cells and identify CD45 as a regulator of PTP{alpha} phosphorylation at tyrosine 789 in T cells.


Received for publication, April 13, 2007 , and in revised form, May 14, 2007.

* This work was supported by the Canadian Institutes of Health Research Grants MOP-49410 (to C. J. P.) and MOP-77712 (to P. J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Recipient of a Bertram Hoffmeister Postdoctoral Fellowship.

2 Recipient of a Child & Family Research Institute (CFRI) studentship and a Harry and Florence Dennison fellowship in Medical Research.

3 Holds a Child & Family Research Institute (CFRI) investigatorship award.

4 To whom correspondence should be addressed: Dept. of Microbiology and Immunology, 2350 Health Sciences Mall, Life Sciences Inst., University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Tel.: 604-822-8980; Fax: 604-822-6041; E-mail: pauline{at}interchange.ubc.ca.


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