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Identification, cloning, and characterization of a novel human T-cell-
specific tyrosine kinase located at the hematopoietin complex on chromosome
5q
S Gibson, B Leung, JA Squire, M Hill, N Arima, P Goss, D Hogg and GB Mills
Oncology Research Division, Toronto General Hospital, Ontario, Canada.
Signal transduction through the T-cell receptor and cytokine receptors on
the surface of T lymphocytes occurs largely via tyrosine phosphorylation of
intracellular substrates. Because neither the T-cell receptor nor cytokine
receptors contain intrinsic kinase domains, signal transduction is thought
to occur via association of these receptors with intracellular protein
tyrosine kinases. Although several members of the SRC and SYK families of
tyrosine kinases have been implicated in signal transduction in
lymphocytes, it seems likely that additional tyrosine kinases involved in
signal transduction remain to be identified. To identify unique T-cell
tyrosine kinases, we used polymerase chain reaction-based cloning with
degenerate oligonucleotides directed at highly conserved motifs of tyrosine
kinase domains. We have cloned the complete cDNA for a unique human
tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural
killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866
bp encoding a protein with a predicted size of 72 Kd, which is in keeping
with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd
protein were detected in T lymphocytes and NK-like cell lines, but were not
detected in other cell lineages. EMT contains both SH2 and SH3 domains, as
do many other intracellular kinases. EMT does not contain the N-terminal
myristylation site or the negative regulatory tyrosine phosphorylation site
in its carboxyterminus that are found in the SRC family of tyrosine
kinases. EMT is related to the B-cell progenitor kinase (BPK), which has
recently been implicated in X-linked hypogammaglobulinemia, to the TECI
mammalian kinase, which has been implicated in liver neoplasia, to the more
widely expressed TECII mammalian kinase, and to the Drosophila melanogaster
Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human
homologue of a recently identified murine interleukin-2 (IL-2)-inducible T
cell kinase (ITK). However, unlike ITK, EMT message and protein levels do
not vary markedly on stimulation of human IL-2-responsive T cells with
IL-2. Taken together, it seems that EMT is a member of a new family of
intracellular kinases that includes BPK, TECI, and TECII. EMT was localized
to chromosome 5q31-32, a region that contains the genes for several growth
factors and receptors as well as early activation genes, particularly those
involved in the hematopoietic system. Furthermore, the 5q31-32 region is
implicated in the genesis of the 5q- syndrome associated with
myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400
WORDS)
Volume 82,
Issue 5,
pp. 1561-1572,
09/01/1993
Copyright © 1993 by The American Society of Hematology
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