Center dnd Raymond and Beverly Sdckler Foundation laboratory, New York, New York 100 I6
Basic fibroblast growth factor (bFCF) is a member of the heparin-binding growth factor (HBCF) family that includes at least seven species. These proteins are potent regulators of a number of cellular processes, including cell division and angiogenesis. Multiple forms of bFCF exist differing only in the length of their NH,-terminal extensions. These species of bFGF also have unique subcellular distributions. The smallest form (1 8 kD) occurs predominantly in the cytosol, while the higher molecular weight forms (22, 22.5, 24 kD) are associated with the nucleus and ribosomes. Here we report that the nuclear localization of the higher molecular weight forms of bFGF derives specifically from the amino acid sequences within the NH,-terminal extension. This has been demonstrated by constructing a chimeric protein containing the NH2-terminal extension of the highest molecular weight form of bFGF fused to p-galactosidase @-gal). After transfection in a transient expression system, the chimeric protein accumulated in the nuclei of transfected cells, while the wild-type P-gal was found predominantly in the cytoplasm.