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Nuclear Transport of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 in Opossum Kidney Cells

Department of Pharmacokinetics and Metabolism (W.L., H.R.W., P.J.F., G.-A.K.), Genentech, Inc., South San Francisco, California 94080; and Department of Medicine (J.F., R.R.), Stanford University and Veteran Affairs Medical Center, Palo Alto, California 94304

Address all correspondence and requests for reprints to: Dr. Gilbert-André Keller, Genentech, Inc., 460 Point San Bruna Boulevard, South San Francisco, California 94080.

When added to cultured opossum kidney cells, IGF-I is internalized and transported to distinct intracellular compartments that depend on the cell location within the monolayer. In resting cells away from the periphery of the monolayer, IGF-I is internalized by a clathrin coated pit pathway and delivered to the endosomal compartment. In contrast, cells growing at the edges of a monolayer or an experimental wound internalize IGF-I by an alternative route which rapidly delivers IGF-I to the nucleus. Similarly to IGF-I, IGFBP-3 is also internalized and accumulates in the endosomal compartment in resting cells whereas it is targeted to the nucleus in proliferating cells. IGFBP-3, which contains a putative nuclear targeting signal, may act as a carrier for IGF-I nuclear transport. The transport of IGF-I and IGFBP-3 to two different compartments may influence their biological activity.

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