Cutting edge: the tyrosine phosphatase SHP-1 regulates thymocyte positive selection.
The binding kinetics of the TCR for its interacting ligand and the nature of the resulting signal transduction event determine the fate of a developing thymocyte. The intracellular tyrosine phosphatase SHP-1 is a potential regulator of the TCR signal transduction cascade and may affect thymocyte development. To assess the role of SHP-1 in thymocyte development, we generated T cell-transgenic mice that express a putative dominant negative form of SHP-1, in which a critical cysteine is mutated to serine (SHP-1 C453S). SHP-1 C453S mice that express the 3.L2 TCR transgene are increased in CD4 single positive cells in the thymus and are increased in cells that express the clonotypic TCR. These data suggest that the expression of SHP-1 C453S results in increased positive selection in 3.L2 TCR-transgenic mice and support a role for SHP-1 thymocyte development.
Plas
D R
DR
Howard Hughes Medical Institute, and Center for Immunology, Department of Pathology, Washington University, St. Louis, MO 63110, USA.
Williams
C B
CB
Kersh
G J
GJ
White
L S
LS
White
J M
JM
Paust
S
S
Ulyanova
T
T
Allen
P M
PM
Thomas
M L
ML
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003545:Cysteine / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D012694:Serine / Q000235:genetics; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; D012694:Serine; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D003545:Cysteine