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

Author:

Li Wenlu1,Fawcett Janet2,Widmer H. Ramon1,Fielder Paul J.1,Rabkin Ralph2,Keller Gilbert-André1

Affiliation:

1. Department of Pharmacokinetics and Metabolism (W.L., H.R.W., P.J.F., G.-A.K.), Genentech, Inc., South San Francisco, California 94080

2. Department of Medicine (J.F., R.R.), Stanford University and Veteran Affairs Medical Center, Palo Alto, California 94304

Abstract

Abstract 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.

Publisher

The Endocrine Society

Subject

Endocrinology

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