Receptors for insulin and other growth factors: rationale for common and distinct mechanisms of cell activation

Abstract

The insulin-like biological activities of serum can now be attributed not only to insulin but also to other structurally related polypeptides (somatomedins or insulin-like growth factors, IGF's). Other polypeptides, like epidermal growth factor-urogastrone (EGF-URO) or platelet-derived growth factor (PDGF) have also been observed to cause "insulin-like" responses in their target cells. The similar biological activities of the polypeptides that are structurally related to insulin (IGF-I, IGF-II) can result either from an activation of their own distinctive receptors (the insulin or IGF-I receptors) or from receptor crossover whereby one polypeptide (e.g., IGF-I) can activate a second receptor system (e.g., the one for insulin). The similarity of cellular responses triggered by the insulin and IGF-I receptors can now be understood in terms of the remarkable similarities between these receptors with regard to their structural, immunologic, and enzymatic (protein tyrosine kinase) properties. Furthermore, the common insulin-like biological activities triggered by other growth factor receptors, like the ones for EGF-URO and PDGF, can now be rationalized in terms of the common protein tyrosine kinase activities and homologous amino acid sequences that these receptors exhibit, along with the receptors for insulin and IGF-I. Although some of the activities of insulin and these growth factors are similar, other actions of these agents are distinct.(ABSTRACT TRUNCATED AT 250 WORDS)