Expression of the p56(Lck) Y505F mutation in CD45-deficient mice rescues thymocyte development.

Abstract:

:Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhibit a block in thymocyte development. To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient mice that express transgenes for the Lck Y505F mutation and the DO11.10 T-cell antigen receptor (TCR). CD4 single-positive T cells developed and accumulated in the periphery. Treatment with antigen resulted in thymocyte apoptosis and the loss of transgenic-TCR-bearing cells. Peripheral CD45-deficient T cells from the mice expressing both transgenes responded to antigen by increasing CD69 expression, interleukin-2 production, and proliferation. These results indicate that thymocyte development requires the dephosphorylation of the inhibitory site in Lck by CD45.

journal_name

Mol Cell Biol

authors

Seavitt JR,White LS,Murphy KM,Loh DY,Perlmutter RM,Thomas ML

doi

10.1128/mcb.19.6.4200

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

4200-8

issue

6

eissn

0270-7306

issn

1098-5549

journal_volume

19

pub_type

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