Fig. 2

The NGBR/Ras signaling pathway promotes angiogenesis. NGBR is a transmembrane protein. NGBR promotes the migration and proliferation of HemSCs by activating the Ras signaling pathway. NGBR acts as a Ras regulator in controlling the growth and differentiation of HemSCs. NGBR activates multiple downstream signaling pathways to promote angiogenesis and migration by activating Ras in HemSCs. NGBR also promotes the cell cycle and ultimately angiogenesis. The three important signaling pathways are as follows: (1) After activating Ras, NGBR further activates the Raf/ERK/MEK/ERK signaling pathway, promotes nuclear gene expression, promotes cell proliferation and migration, and promotes G1 to S phase transition in the cell cycle. (2) NGBR activates the Ras/PI3K/PAK/MEKK1 signaling pathway to promote cell proliferation and migration. (3) NGBR can also activate the AKT/ERK/P53/p21 signaling pathway, promote cell proliferation and migration, and thus promote angiogenesis. In addition, several important growth factors (VEGF, PDGF, FGF2, and EGF) promote cell proliferation and migration by binding to their respective RTK receptors to activate protein tyrosine kinase activity within the receptors, which then activates Ras and Ras-dependent signal transduction cascades in the cell membrane. NGBR regulates the Ras signaling pathway, while PTK growth factors activate HemSC proliferation and migration. Ras, as a core gene in the NGBR pathway, plays an important role in promoting vascular growth. Phosphatidylinositol-3 kinase (PI3K), p21-activated kinase (PAK), mitogen-activated kinase kinase 1(MEKK1), platelet-derived growth factor (PDGF), fibroblast growth factor 2 (FGF2), epidermal growth factor (EGF).