Gab Docking Proteins in Cardiovascular Disease, Cancer, and Inflammation

Figure 3

Schematic illustration of the role of Gab1 in postnatal angiogenesis and endothelial homeostasis. Hypoxic tissues secrete growth factors, such as HGF and VEGF, which stimulate their specific receptors on endothelial cells (inset). The activation of c-Met receptors leads to the tyrosine phosphorylation of Gab1 and thereby to the subsequent complex formation of Gab1 with both SHP2 and p85. Whereas the formation of the Gab1-SHP2 complex is required for the activation of ERK1/2 and ERK5, the Gab1-p85 complex is essential for the activation of AKT in response to HGF. The ERK1/2 and ERK5 pathways contribute to the upregulation of early growth response 1 (Egr1) and Kruppel-like factor 2 (KLF2). On the other hand, activation of the VEGFR2 receptors leads to the tyrosine phosphorylation of Gab1, and to the subsequent formation of the Gab1-SHP2 complex, which causes the activation of protein kinase A (PKA) and endothelial nitric oxide synthase (eNOS). Collectively, current findings indicate that Gab1 is an essential component of postnatal angiogenesis after ischemia.