8 IGF-I Receptor Signaling in Cell Growth and Proliferation

Abstract

This chapter focuses on the role of the type 1 insulin-like growth factor receptor (IGF-IR) in the control of cell growth (cell size) and proliferation. I present a model of cell growth and proliferation built around the IGF-IR and its signaling pathways. This, of course, does not mean that cell growth and proliferation are exclusive prerogatives of the IGF-IR. It means that, using the IGF-IR and its pathways, one can build a model of cell growth and proliferation, whose features can be extended to and combined with other growth factor models. The IGF-IR is not an absolute requirement for growth and proliferation, either in vivo or in vitro, but it plays a significant role, especially in vivo. That cells do not require the IGF-IR for growth in culture is demonstrated by the ability of mouse embryo fibroblasts (MEFs) derived from mice with a targeted disruption of the IGF-IR genes (Liu et al. 1993) to grow and proliferate in serum-supplemented medium (Sell et al. 1993). The same is true in vivo, as discussed below. In this perspective, the IGF-IR is one of several growth factor receptors that play an important role in the physiology of cell growth and proliferation. I begin with a brief background on the IGF-IR itself. For detailed information on the basic aspects of the IGF-IR—its structure, functions, and signaling pathways—the reader is referred to the reviews by Blakesley et al. (1999) and Baserga (2000), and to the book edited by Rosenfeld and Roberts (1999).

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