We have used serum-deprived cultures of wild type and genetically modified PC12 cells to investigate the molecular mechanisms by which monosialoganglioside (G) rescues neuronal cells from apoptotic death elicited by withdrawal of trophic support. Our findings indicate that G-promoted survival can be mediated in part by the Trk NGF receptor as well as by TrkB, and potentially by tyrosine kinase receptors for additional neurotrophic growth factors. Experiments employing K-252a, an inhibitor of Trk kinases, and PC12 cells overexpressing a dominant inhibitory form of Trk both indicate that a portion of the survival-promoting activity of G is evoked by receptor dimerization and autophosphorylation. In consonance with this we find that G stimulates Trk tyrosine autophosphorylation and Trk-associated protein kinase activity. These observations may provide a mechanism to account for the reported in vitro and in vivo trophic actions of G.

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