this characteristic is an important feature of the 
TdT promoter and whether it contributes to appro- 
priate transcriptional regulation in developing 
lymphocytes. 
Dr. Smale is also Assistant Professor of Microbi- 
ology and Immunology and a member of the Mo- 
lecular Biology Institute at the University of Cali- 
fornia, los Angeles, School of Medicine. 
Articles 
Lo, K., Landau, N R., and Smale, S.T. 1991. LyF-1, a 
transcriptional regulator that interacts with a 
novel class of promoters for lymphocyte-specific 
genes. Mol Cell Biol 1 1 :5229-5243. 
O'Shea-Greenfield, A., and Smale, S.T. 1992 
Roles of TATA and initiator elements in determin- 
ing the start site location and direction of RNA 
polymerase II transcription. / Biol Chem 267: 
1391-1402. 
Sakaguchi, M., Zenzie-Gregory, B., Groopman, 
J.E., Smale, S.T., and Kim, S.Y. 1991 ■ Alternative 
pathway for induction of human immunodefi- 
ciency virus gene expression-, involvement of 
the general transcription machinery. / Virol 65: 
5448-5456. 
Zenzie-Gregory, B., O'Shea-Greenfield, A., and 
Smale, S.T. 1992. Similar mechanisms for tran- 
scription initiation mediated through a TATA box 
or an initiator element. / iJ/o/ Chem 267:2823- 
2830. 
CONTROL OF CELLULAR REGULATION BY PROTEIN-TYROSINE PHOSPHATASES 
Matthew L. Thomas, Ph.D., Assistant Investigator 
Dr. Thomas and his colleagues are interested in 
defining the interactions and functions of protein- 
tyrosine phosphatases (PTPases) expressed by cells 
of the immune system. Studies in recent years from 
this and several other laboratories have demon- 
strated that PTPases are a large, diverse group of en- 
zymes critical in the regulation of the cell cycle, 
differentiation, and activation. The Thomas group's 
research effons are focused on determining the 
function, characterization, and expression of indi- 
vidual PTPases. 
Characterization of Hematopoietic 
Intracellular PTPases 
Lymphocyte activation induced by engagement of 
either the T cell antigen receptor or membrane im- 
munoglobulin results in a rapid change in tyrosine 
phosphorylation. The exact kinases and phospha- 
tases responsible for regulating antigen-induced ac- 
tivation are not known, although members of the 
Src-family tyrosine kinases and the transmembrane 
PTPase CD45 have all been implicated. Defining the 
coordinate interaction between the kinases and 
phosphatases in regulating cellular functions is em- 
phasized in the Thomas group's research activities. 
Initial studies characterized the hematopoietic- 
specific CD45 PTPase. Subsequently a large number 
of cDNAs with significant sequence similarity to 
CD45 were identified from an invertebrate species, 
Styela plicata. This indicated that the PTPase family 
is extensive and provided the basis for identifying 
additional PTPases expressed by hematopoietic 
cells. 
Screens of mouse tissues and cell lines revealed 
several novel phosphatases, a limited number of 
which were primarily expressed by cells of the im- 
mune system. One of these PTPases, SHP, was pre- 
dicted to be intracellular. Development of a specific 
antiserum allowed the demonstration that SHP is a 
cytosolic protein. SHP is expressed by several dis- 
tinct lineages of leukocytes, including macro- 
phages, and by T and B lymphocytes. The pattern of 
SHP expression within tissues was examined by in 
situ hybridization, using a complementary RNA- 
derived probe. SHP is expressed widely in lymphoid 
tissues, but more abundantly in the medulla of the 
thymus, with its more mature thymocytes, and in 
follicles of spleen and lymph nodes, areas rich in B 
cells. 
The structure of SHP predicts that it may be di- 
rectly involved in regulating signal transduction. 
The amino-terminal domain contains two tandem 
SH2 domains. SH2 domains have been demonstrated 
to bind phosphorylated tyrosine or serine residues, 
thus providing a means by which phosphorylation 
results in interactions with other proteins. It is 
likely that there are specific interactions for each 
SH2 domain. Dr. Thomas's group expressed bacte- 
rial fusion proteins containing SHP SH2 domains 
and demonstrated specific interactions with a subset 
IMMUNOLOGY 
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