Protein-Tyrosine Phosphatases and the Control of Lymphocyte Activation 
examine the expression of the protein by var- 
ious leukocyte populations, the extent of post- 
translational modification, and the ability of the 
antibody to induce changes in lymphocyte activa- 
tion and proliferation. 
PEP and SHP are both intracellular protein- 
tyrosine phosphatases expressed primarily by 
leukocytes. PEP contains a large carboxyl-termi- 
nal extension following the phosphatase domain. 
This region is unusual when compared with other 
intracellular phosphatases, in that it contains se- 
quences indicative of nuclear localization and 
rapid protein turnover. By tagging the protein 
with a sequence that can be traced, we have ob- 
tained preliminary results indicating that PEP 
does indeed localize to the nucleus. It is possible, 
therefore, that PEP is involved in regulating gene 
transcription or other nuclear functions. 
SHP contains two src-homology region-2 
(SH2) domains linked in tandem immediately 
amino terminal to the PTPase catalytic domain. 
SH2 domains are found in proteins involved in 
transducing mitogenic signals, such as all the 
nonreceptor protein-tyrosine kinases, the p21"* 
GTPase-activating protein, and the 7-isoform of 
the phosphatidylinositol-specific phospholipase 
C. Functionally, SH2 domains bind phosphory- 
lated tyrosine residues. Thus a protein that con- 
tains SH2 domains serves to amplify and direct 
the biochemical pathway of a response that is in- 
duced by an initial increase in tyrosine phosphor- 
ylation. Recent results indicate that the SHP SH2 
domains are capable of binding a low-molecular- 
weight phosphotyrosine protein. The existence 
of a phosphatase that contains SH2 domains sug- 
gests that SHP may serve to modulate kinase-in- 
duced signals. We are examining the plausibility 
of this model by identifying the specific proteins 
with which SHP interacts. 
Through an understanding of how protein- 
tyrosine phosphatases effect lymphocyte activa- 
tion, we hope to gain a more thorough knowledge 
of the biochemical steps involved in control- 
ling and regulating an immune response. The 
functional characterization of multiple protein- 
tyrosine phosphatases expressed by lymphocytes 
has allowed us to define steps in which members 
of this family function in lymphocyte activation. 
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