A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.
Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.
Partanen
J
J
Department of Virology, University of Helsinki, Finland.
Armstrong
E
E
Mäkelä
T P
TP
Korhonen
J
J
Sandberg
M
M
Renkonen
R
R
Knuutila
S
S
Huebner
K
K
Alitalo
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000737:chemistry*; D004815:Epidermal Growth Factor; D005353:Fibronectins; D005796:Genes / Q000235:genetics; D007074:Immunoglobulin G; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014162:Transfection
D005353:Fibronectins; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases