TEK

TEK2b, also known as Tie-2 or TEK, is a 145 kD type I transmembrane protein. It is a member of the receptor tyrosine kinase (RTK) family of proteins and is expressed by endothelial cells and their progenitors, quiescent hematopoietic stem cells (HSCs), and a subpopulation of monocytes. Angiopoietin-1 (Ang-1) is an activator of TEK2b to promote, maintain, and stabilize mature vessels and to maintain HSCs in the quiescent state. Ang-2 is another ligand of TEK2b, which is involved in postnatal angiogenesis and in antagonizing the effects of Ang-1. Tie-2 also binds to Ang-4.

TIE1

• Tie-1/Tie (tyrosine kinase with Ig and EGF homology domains 1) and Tie-2/Tek comprise a receptor tyrosine kinase (RTK) subfamily with unique structural characteristics: two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains and followed by three fibronectin type III-like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region. These receptors are expressed primarily on endothelial and hematopoietic progenitor cells and play critical roles in angiogenesis, vasculogenesis and hematopoiesis.
• Human Tie-1 cDNA encodes a 1138 amino acid (aa) residue precursor protein with a 24 residue putative signal peptide, a 735 residue extracellular domain and a 354 residue cytoplasmic domain. Ligands which bind and activate Tie-1 have not been identified. Based on gene-targeting studies, the in vivo functions of Tie-1 have been shown to be related to endothelial cell differentiation and the maintenance of integrity of the endothelium.

Gene targeting strategy for B-hTEK/hTIE1 mice.

Exons 2~14 of the mouse Tek gene that encode the full-length protein were replaced by human TEK exons 2~14 in B-hTEK/hTIE1 mice.

Exons 2~14 of the mouse Tie1 gene that encode the full-length protein were replaced by human TIE1 exons 2~14 in B-hTEK/hTIE1 mice.

Strain specific TEK expression analysis in homozygous B-hTEK/hTIE1 mice by flow cytometry. Lung were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTEK/hTIE1 mice (H/H, H/H), and analyzed by flow cytometry with anti-TEK antibody. mTEK was detectable in wild-type, hTEK was detectable in wild-type and homozygous B-hTEK/hTIE1 mice, as the antibody is cross-recognize both human and mouse TEK.

Strain specific analysis of TEK mRNA expression in wild-type C57BL/6 mice and B-hTEK/hTIE1 mice by RT-PCR. Lung RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hTEK/hTIE1 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human TEK primers. Mouse Tek mRNA was detectable only in wild-type C57BL/6 mice. Human TEK mRNA was detectable only in homozygous B-hTEK/hTIE1 mice but not in wild-type mice.

Strain specific analysis of TIE1 mRNA expression in wild-type C57BL/6 mice and B-hTEK/hTIE1 mice by RT-PCR. Lung RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hTEK/hTIE1 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human TIE1 primers. Mouse Tie1 mRNA was detectable only in wild-type C57BL/6 mice. Human TIE1 mRNA was detectable only in homozygous B-hTEK/hTIE1 mice but not in wild-type mice.