International Immunology, Vol 10, 1217-1227, Copyright © 1998 by Oxford University Press
A Sato, A Iwama, N Takakura, H Nishio, GD Yancopoulos and T Suda
TEK, or TIE-2, is a receptor tyrosine kinase (RTK) that is known as a
functioning molecule of vascular endothelial cells. TEK comprises a
subfamily of RTK with TIE, and these two receptors play critical roles in
vascular maturation, maintenance of integrity and remodeling. We generated
mAb against the extracellular domain of human TEK protein to elucidate its
expression pattern in human hematopoietic cells. Flow cytometric analysis
of bone marrow cells revealed that TEK was expressed in 27% of CD34+ cells,
20% of c-KIT+ cells and 26% of CD34+CD38- cells, indicating that TEK is
expressed in a subset of primitive hematopoietic stem cells (HSC). TEK was
also expressed in 20% of CD19+ B lymphocytes but not in other
lineage-committed cells. Progenitor assays in methylcellulose culture
showed that CD34+TEK+ cells formed significantly less BFU-E and CFU-Mix
than CD34+TEK- cells, but there was no difference in the number of CFU-GM
between these two populations. Two recently identified TEK ligands, termed
Angiopoietin-1 and -2, bound to TEK with similar affinities, and
Angiopoietin-1 effectively induced TEK phosphorylation in hematopoietic
cells. Angiopoietin-2 also induced a low level of TEK phosphorylation and
weakened the phosphorylation induced by Angiopoietin-1, suggestive of an
elaborate regulator of the TEK-TEK ligand signaling pathway. Although
neither ligands affected the proliferation of TEK-transfected hematopoietic
cells or the colony formation of CD34+TEK+ bone marrow cells, both promoted
the adhesion of TEK-transfected hematopoietic cells to a collagen matrix or
a layer of bone marrow stromal cells. These findings indicate that the
TEK-TEK ligand signaling pathway is regulated in a refined manner and is
involved in hematopoietic cell- microenvironment interaction.
ARTICLES
Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Honjo, Japan.
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