The angiopoietins, Ang-1 and Ang-2, are growth factors that play a key role in vessel homeostasis, angiogenesis, and vascular permeability via interacting with the Tie-2 transmembrane receptor tyrosine kinase.Ang-1 plays a protective role in pathological angiogenesis and supports a quiescent, mature vessel phenotype.  Ang-1 has been shown to suppress VEGF-A induced neovascularization in double transgenic mice coexpressing Ang-1 and VEGF-A. Ang-2 is involved in vascular leakage, abnormal vessel structure, and shown to enhance proinflammatory signals in endothelial cells. The acronym Tie stands for tyrosine kinase with immunoglobulin and EGF homology domains. Tie-1 and Tie-2 possess a unique extracellular structure consisting of two immunoglobulin motifs at the N-terminus, followed by three EGF homology domains, another immunoglobulin motif, three fibronectin type III-like repeats, a transmembrane domain and a catalytic carboxy-terminal tyrosine kinase domain responsible for intracellular signal transduction. 
Activated Tie-2 receptor stimulates a number of intracellular signaling pathways, notably the phosphoinositide 3-kinase (PI3K) pathway which promotes EC survival and NO synthesis by activation of the protein kinase B (PKB)/Akt, eNOS, mitogen activated protein kinase (MAPK) and Dok-R/Nck/Pak pathways. Other signaling events associated with Tie-2 activation include the recruitment of ABIN-2 (A20-binding inhibitor of NFjB-2), which suppresses NFjB activity and protects EC from apoptosis. Ang-2 is able to bind several integrin family members in Tie-2-negative ECs and to induce focal adhesion kinase (FAK) phosphorylation. Such Tie-2-independent signal promotes the activation of the small GTPase RAC1, cell migration and sprouting angiogenesis. Ang-2 can have a direct pro-angiogenic Tie-2-independent role by binding integrins.

References

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