The AMIGO2–PDK1–Akt signaling pathway. (A) This model proposes that the direct binding of AMIGO2 to the PDK1 PH domain enhanced the activation of PDK1 and Akt in the plasma membrane, which resulted in increased EC viability, adhesion, migration, and angiogenesis. (B) Loss of AMIGO2 attenuated the phosphorylation of PDK1 and Akt and EC survival and adhesion. (C) PTD-A2, a specific peptide in the C-terminal region of AMIGO2, effectively abrogated the phosphorylation of PDK1 and Akt, cell survival, OIR-induced angiogenesis, tumor angiogenesis, and tumor growth. P, phosphorylation.