Signaling pathways involved in the pathogenesis of venous malformations

Binding of ANG-1 to the tyrosine kinase receptor TIE2 activates the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway. mTOR exists as two complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Activated PI3K phosphorylates AKT on threonine 308, leading to partial activation of AKT. Full activation of AKT requires a second phosphorylation that is induced by mTORC2. AKT is thereby able to regulate different transcription factors and regulate platelet-derived growth factor (PDGF)-beta production.