Proto-oncogenes and signaling processes in neural tissues.

The study of ubiquitously expressed proto-oncogenes or tumor suppressor genes provided important insights into the second messenger signaling pathways common to neural and non-neural tissues. Therefore, it is expected that the analysis of proto-oncogenes expressed in neural tissues should probe into neurotrophic and neurotransmitter receptors, ion channels and other molecules involved in processes underlying basic physiological functions of the nervous system. This expectation is fulfilled by ample experimental evidence. Using the trk, abl and src families of tyrosine kinase encoded proto-oncogenes, we discuss here new insights into the structural and functional organization of neural tissues gained from the molecular and genetic analyses of these genes and their products. Special attention is given to the description of initial steps of signaling through the Trk receptors in response to neurotrophic factors of the Nerve Growth Factor family. The genetic analysis of the Drosophila abl gene product identified new gene products that interact with the Abl protein. This analysis illuminates the power of Drosophila genetics in dissecting components of a signal transduction pathway. The Src-family of non-receptor type protein-tyrosine kinases is discussed from the point of functional redundancy as revealed by targeted gene disruption and expression studies. The recent progress in the field of proto-oncogenes has been impressive and it is expected that proto-oncogenes will continue to provide valuable tools in the study of the complex signaling pathways that underlie the physiological functions of the central nervous system.