Nuclear transport of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in opossum kidney cells.
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.
Li
W
W
Department of Pharmacokinetics and Metabolism, Genentech, Inc., South San Francisco, CA 94080, USA.
Fawcett
J
J
Widmer
H R
HR
Fielder
P J
PJ
Rabkin
R
R
Keller
G A
GA
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009893:Opossums
D005456:Fluorescent Dyes; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I