This chapter will explore the role of survival factors in suppression of apoptosis, and illustrate how survival signals play a critical role in the survival of both normal and tumor cells. Survival factors necessary for the development and maintenance of the nervous system and hemopoietic system will be surveyed. This will be followed by a detailed discussion of the role of insulin-like growth factor I (IGF-I) and its receptor in suppression of apoptosis. The importance of survival signals from the IGF-IR for development and tumorigenesis will be discussed, and results of a mutational analysis of the receptor to assign domains necessary for suppression of apoptosis will be summarized. Finally, a discussion of the signal transduction pathways involved in survival factor-signaling will review the roles played by PI-3 kinase and AKT and speculate on how activation of these kinases by survival factors might regulate the apoptotic pathway.
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