FIG. 6.

Proposed model for the selective in vivo role of Tie2 signaling pathways. Signal transduction pathways emanating from Tyr¹¹⁰⁰ on Tie2 are required for cardiac development and early hematopoietic and endothelial cell development in the P-Sp region. PI3-kinase activation in response to Ang1 is mediated through Tyr¹¹⁰⁰. Additionally, the adaptor proteins ShcA and Grb7, both of which can associate with the cytosolic FAK kinase, are also recruited to Tyr¹¹⁰⁰. In contrast, signaling from residues other than Tyr¹¹⁰⁰, such as Tyr¹¹⁰⁶, may govern perivascular cell recruitment and/or adhesion to nascent vessels to promote vascular integrity. The formation of a signaling complex of Dok-R, RasGAP, Nck, and Pak occurs at Tyr¹¹⁰⁶. The SH2 domain containing tyrosine phosphatase Shp2 has been proposed to bind to Tyr¹¹¹¹, although the functional significance of this interaction remains unclear. Additional important tyrosine residues on Tie2, including juxtamembrane tyrosine residue 814 (which may recruit Shp2 and/or Grb14) and tyrosine residue 990 in the activation loop, are not shown.