Early events in neurotrophin signalling via Trk and p75 receptors.

Biological responses to neurotrophins appear to be mediated by multiple signalling pathways. These emanate from, and are regulated by, the contributions of both Trk and p75 receptors. Early events in Trk signalling are becoming more clearly defined and point to cooperate interaction of both Ras-dependent and Ras-independent pathways. Work over the past year has clarified the steps by which Trk receptor occupation leads to Ras activation and has highlighted the required roles of Ras and extracellular signal regulated kinases in certain neurotrophin responses, including neurite outgrowth. Pharmacologic and mutagenesis studies have additionally supported the importance of the phosphatidylinositol-3' kinase and SNT protein pathways in neurotrophin signalling. Although many findings point to clear involvement for p75 in neurotrophin signalling, the molecular mechanisms by which these occur are just beginning to be identified. Recent studies indicate that p75 dramatically influences Trk activity and ligand interactions, and may mediate signals through the ceramide second-messenger pathway.