Inability of the acidic fibroblast growth factor mutant K132E to stimulate DNA synthesis after translocation into cells.

The Journal of Biological Chemistry
O KlingenbergSjur Olsnes

Abstract

Acidic fibroblast growth factor (aFGF) is a potent mitogen. It acts through activation of specific cell surface receptors leading to intracellular tyrosine phosphorylation cascades, but several reports also indicate that aFGF enters cells and that it has an intracellular function as well. The aFGF(K132E) mutant binds to and activates fibroblast growth factor receptors equally strongly as the wild-type, but it is a poor mitogen. We demonstrate that aFGF(K132E) enters NIH 3T3 cells and is transported to the nuclear fraction like wild-type aFGF. A fusion protein of aFGF(K132E) and diphtheria toxin A-fragment (aFGF(K132E)-DT-A) and a similar fusion protein containing wild-type aFGF (aFGF-DT-A) were reconstituted with diphtheria toxin B-fragment. Both fusion proteins were translocated to the cytosol by the diphtheria toxin pathway and subsequently recovered from the nuclear fraction. Whereas translocation of aFGF-DT-A stimulated DNA synthesis in U2OSDR1 cells lacking functional fibroblast growth factor receptors, aFGF(K132E)-DT-A did not. The mutation disrupts a protein kinase C phosphorylation site in the growth factor making it unable to be phosphorylated. The data indicate that a defect in the intracellular action of aFGF(K132E) ...Continue Reading

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Citations

Nov 15, 2007·Applied Microbiology and Biotechnology·Yadong HuangXiaokun Li
Jul 4, 2009·The Journal of Biological Chemistry·Malgorzata ZakrzewskaSjur Olsnes
Dec 6, 2003·Molecular Biology of the Cell·Jedrzej MałeckiSjur Olsnes
Dec 3, 2004·Molecular Biology of the Cell·Antoni WiedłochaSjur Olsnes
Jul 30, 2002·The EMBO Journal·Camilla Skiple SkjerpenSjur Olsnes
May 16, 2014·Journal of Signal Transduction·Rajesh RajuHarsha Gowda
Feb 23, 2008·Critical Reviews in Clinical Laboratory Sciences·Malgorzata ZakrzewskaAntoni Wiedlocha
Dec 26, 2001·The Journal of Biological Chemistry·Yoshihiko KishimaHideji Nakamura
Jun 11, 1999·The Journal of Biological Chemistry·O KlingenbergS Olsnes
Dec 31, 2002·Physiological Reviews·Sjur OlsnesAntoni Wiedłocha
Jul 10, 2007·The Journal of Biological Chemistry·Trine NilsenAntoni Wiedłocha
Dec 21, 2006·Biochemistry·Malgorzata ZakrzewskaJacek Otlewski

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