Dimerization of cell surface receptors in signal transduction

Introduction Cell growth, differentiation, migration, and apoptosis are in part regulated by polypeptide growth factors or cytokines. As these factors are unable to pass the hydrophobic cell membrane, a fundamental question is how they transduce their signals into the cell. Growth factors and cytokines exert their effects via binding to cell surface receptors; results obtained during recent years have given ample evidence that such receptors often are activated by ligand-induced dimerization or oligomerization. Moreover, the elucidation of intracellular signal transduction pathways have revealed that the activity of several components in these pathways are also regulated by dimerization. For instance, certain of the cytoplasmic signal transduction molecules dimerize after activation, and the active form of transcription factors are often dimers. It thus appears that dimerization is a mechanism of general applicability for the regulation of signal transduction. This review focuses on the role of dimerization of cell surface receptors in signal transduction. Dimerization or oligomerization have been shown to occur after binding of several polypeptide hormones, cytokines, growth factors, or growth inhibitors to their receptors. Examples include protein-tyrosine kinase receptors, cytokine receptors, antigen receptors, receptors for tumor necrosis factor (TNF) and related factors, and serine/threonine kinase receptors (Figure 1; Table 1). There are, however, many variations on the theme, as will be discussed below.