**5.1 Tek**

Tie2, encoded by the *TEK* gene, is an RTK expressed predominantly on endothelial cells, but they also provide crucial functions in the maintenance of quiescence and self-renewal capacity of the HSCs (Arai et al., 2004). The interaction between Tie2 and angiopoietin-1 (Ang-1), its ligand, has been shown to promote ubiquinylation of Tie2 by Cbl and receptor internalization (Wehrle et al., 2009). Structurally, the cytoplasmic domain of Tie2 does not contain any tyrosine residues that match the canonical Cbl(TKB) recognition sequence. However, activated Tie2 is known to bind Grb2 (Huang et al., 1995), thus may interact with Cbl indirectly through this adaptor.
