Fibroblast Growth Factor-2 Binds to the Regulatory β Subunit of CK2 and Directly Stimulates CK2 Activity toward Nucleolin

doi:10.1074/jbc.271.40.24781

Fibroblast Growth Factor-2 Binds to the Regulatory β Subunit of CK2 and Directly Stimulates CK2 Activity toward Nucleolin*

From the ^‡ Laboratoire de Biologie Moléculaire Eucaryote, CNRS, 118 route de Narbonne, 31062 Toulouse Cedex, France and the
^§ CEA, Biochimie des Régulations Cellulaires Endocrines, INSERM U244, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France

^¶ To whom correspondence should be addressed. Tel.: 33-61-33-59-49; Fax: 33-61-33-58-86.

Abstract

The presence of fibroblast growth factor-2 (FGF-2) in the nucleus has now been reported both in vitro and in vivo, but its nuclear functions are unknown. Here, we show that FGF-2 added to nuclear extract binds to protein kinase CK2 and nucleolin, a CK2 natural substrate. Added to baculovirus-infected cell extracts overexpressing CK2 or its isolated subunits, FGF-2 binds to the enzyme through its regulatory β subunit. Using purified proteins, FGF-2 is shown to directly interact with CK2 and to stimulate CK2 activity toward nucleolin. Furthermore, a mitogenic-deficient FGF-2 mutant protein has an impaired ability to interact with CK2 and to stimulate CK2 activity using nucleolin as substrate. We propose that in growing cells, one function of nuclear FGF-2 is to modulate CK2 activity through binding to its regulatory β subunit.

Footnotes

↵* This work was supported by grants from the Centre National de la Recherche Scientifique, Ligue Nationale contre le Cancer, Association pour la Recherche contre le Cancer, and the Conseil Régional de Midi-Pyrénées. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

FGF

fibroblast growth factor

biotFGF-2

biotinylated FGF-2

Δ1 FGF-2

mutant form of FGF-2 that corresponds to a deletion of 6 residues: Lys²⁷ to Leu³²

WT FGF-2

wild-type FGF-2

ABAE cells

adult bovin aortic endothelial cells

CHO cells

Chinese hamster ovary cells

FM3A cells

murin fibroblast cells

EGF

epidermal growth factor

NGF

nerve growth factor

H₂OmQ

H₂O milli-RO water system.
- Received January 24, 1996.
- Revision received June 24, 1996.