Abstract
The three high molecular weight (HMW) forms of fibroblast growth factor-2 (FGF-2) have a distinct intracellular localization and differentially affect cell mobility and growth compared with the fourth 18-kDa form. To characterize further the effects of the 18-kDa and HMW forms of FGF-2, we have examined their ability to modulate integrin expression. Transfected NIH 3T3 cells expressing only 18-kDa FGF-2 exhibited increased cell surface levels of alpha5beta1, whereas cells expressing only HMW FGF-2 exhibited cell surface alpha5beta1 levels similar to parental cells. When cells synthesizing 18-kDa FGF-2 were transfected with a cDNA encoding a dominant negative FGF receptor, alpha5beta1 cell surface levels decreased. Immunoprecipitation of biosynthetically labeled cells indicated that expression of 18-kDa FGF-2 increased the biosynthesis and rate of maturation of alpha5. Northern blot analysis showed that 18-kDa FGF-2 increases the level of the alpha5 subunit mRNA but does not affect beta1 subunit transcript levels. Experiments utilizing luciferase reporter gene activity revealed increased alpha5 promoter activity in cells expressing 18-kDa FGF-2 indicating that the enhanced alpha5 transcript level is due to modulation of the transcription rate. Therefore, interaction of 18-kDa FGF-2 with FGF receptors results in changes in alpha5beta1 biosynthesis and processing. In contrast, endogenous expression of HMW FGF-2 does not mediate this effect.
Highlights
To characterize further the effects of the 18-kDa and high molecular weight (HMW) forms of Fibroblast growth factor-2 (FGF-2), we have examined their ability to modulate integrin expression
Endogenous 18-kDa FGF-2 but Not HMW FGF-2 Increases Surface 1 Integrin Levels—Previously we demonstrated that integrin expression in cultured endothelial cells could be modulated by exogenous FGF-2 [23]
The data reported in this paper show that the pattern of expression of 1 integrins at the cell surface of NIH 3T3 cells is influenced by endogenous 18-kDa FGF-2 but not by HMW FGF-2
Summary
To characterize further the effects of the 18-kDa and HMW forms of FGF-2, we have examined their ability to modulate integrin expression. Four distinct high affinity tyrosine kinase plasma membrane receptors encoded by four different genes have been described for FGF [1, 11]. Each of these genes encodes multiple variants derived from alternative mRNA splicing [12,13,14,15]. Treatment of endothelial cells with FGF-2 caused significant changes in the surface expression of nine different integrins [23]. Modulation of integrins may be one of the FGF-2-induced effects on endothelial cells during
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