Significance of SGK1 as a protein kinase transcriptionally regulated by ALK1 signaling in vascular endothelial cells

Bone morphogenetic protein 9 (BMP9)/BMP10-ALK1 receptor signaling is essential for endothelial differentiation and vascular morphogenesis and is implicated in hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension [1]. The ALK1 signal induces SMAD1/5/9-dependent transcription of its own signaling components, transcription factors and membrane ligands/receptors. In addition, we recently identified Serum/glucocorticoid-regulated kinase 1 (SGK1) to be transcriptionally regulated by ALK1 signaling in vascular endothelial cells [2] (Fig. 45.1a). The ALK1 signal is known to evoke post-translational activation of protein kinases such as TAK1 and ERK as a non-canonical pathway, but SGK1 is the first example of protein kinases whose expression is controlled by the SMAD-dependent pathway (Fig. 45.1b).