A model describing the suggested effect of plexin-A4 on signal transduction induced by selected semaphorins and growth factors in endothelial cells. Our results suggest that plexin-A4 transduces or modulates the transduction of diverse signals. (A) Plexin-A4 forms a tripartite complex with plexin-A1 and neuropilin-1. This complex transduces growth inhibitory signals of sema3A that inhibit ERK1/2 phosphorylation as well as signals that result in inhibition of cell adhesion and affect the organization of the cytoskeleton as a result of the activation of the GAP domain of these plexins (reviewed in Neufeld and Kessler¹⁷ ). (B) Plexin-A4 is also able to form complexes with the FGF receptors FGFR1 and FGFR2 and with the VEGF receptor VEGFR-2. This association enhances bFGF and VEGF-induced signal transduction mediated by their respective tyrosine-kinase receptors. In addition, our results suggest that plexin-A4 transduces pro-proliferative signals induced by sema6B. Lastly, when the expression of plexin-A4 in endothelial cells is inhibited we find that the cells undergo profound changes in the organization of their cytoskeleton that are accompanied by changes in the activation state of Rac-1, suggesting that signals transduced by plexin-A4 are important for the maintenance of the correct organization of the cytoskeleton of the endothelial cells.