title: Ligand-mediated endocytosis and trafficking of the insulin-like growth factor receptor I and insulin receptor modulate receptor function.
abstract: The insulin-like growth factor system and its two major receptors, the IGF receptor I (IGF-IR) and IR, plays a central role in a variety of physiological cellular processes including growth, differentiation, motility, and glucose homeostasis. The IGF-IR is also essential for tumorigenesis through its capacity to protect cancer cells from apoptosis. The IR is expressed in two isoforms: the IR isoform A (IR-A) and isoform B (IR-B). While the role of the IR-B in the regulation of metabolic effects has been known for several years, more recent evidence suggests that the IR, and in particular the IR-A, may be involved in the pathogenesis of cancer. Ligand-mediated endocytosis of tyrosine-kinases receptors plays a critical role in modulating the duration and intensity of receptors action but while the signaling pathways induced by the IGF-IR and IR are quite characterized, very little is still known about the mechanisms and proteins that regulate ligand-induced IGF-IR and IR endocytosis and trafficking. In addition, how these processes affect receptor downstream signaling has not been fully characterized. Here, we discuss the current understanding of the mechanisms and proteins regulating IGF-IR and IR endocytosis and sorting and their implications in modulating ligand-induced biological responses.
authors.affiliation: Departments of Urology, Sydney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA , USA ; Department of Health Sciences and Endocrinology, University Magna Graecia of Catanzaro , Catanzaro , Italy.
authors.forename: Alaide
authors.initials: A
authors.lastname: Morcavallo
authors.affiliation: Departments of Urology, Sydney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA , USA ; Department of Health Sciences and Endocrinology, University Magna Graecia of Catanzaro , Catanzaro , Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Stefanello
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Sydney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA , USA ; Cancer Cell Biology and Signaling Program, Sydney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA , USA.
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.affiliation: Department of Health Sciences and Endocrinology, University Magna Graecia of Catanzaro , Catanzaro , Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Belfiore
authors.affiliation: Departments of Urology, Sydney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA , USA ; Biology of Prostate Cancer Program, Sydney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA , USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Morrione
keywords: IGF-IR; IR; endocytosis; signaling; trafficking