Figure 6. Schematic cartoon showing regulatory signaling pathways mediated by SEMA3F-NRP2/Plexin A1 interactions.

SEMA3F binds to the NRP2-Plexin A1 complex and associates with PTEN to inactivate PI-3K and mTORC2/Akt-dependent signaling. Receptor-mediated signals may also inactivate mTORC2/Akt signaling via PTEN-independent mechanisms in tumor cell lines. Functionally, these regulatory/pro-resolution signals suppress cell proliferation, migration, cytoskeletal stress fiber rearrangement and cell survival. Our previous findings demonstrate that SEMA3F also inhibits cytoskeleton structure in part by inactivating RhoA through both the ABL2 kinase and p190RhoGAP⁶; the current studies show that the inactivation of RhoA and cytoskeletal stress fiber rearrangement is also mediated via the inhibition of mTORC2.