INTEGRIN REGULATION BY ENDOGENOUS EXPRESSION OF 18-KDA FIBROBLAST GROWTH FACTOR-II

The three high molecular weight (HMW) forms of fibroblast growth facto r-2 (FGF-2) have a distinct intracellular localization and differentia lly affect cell mobility and growth compared with the fourth 18-kDa fo rm. 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 inc reased cell surface levels of alpha 5 beta 1, whereas cells expressing only HMW FGF-2 exhibited cell surface alpha 5 beta 1 levels similar t o parental cells. When cells synthesizing 18-kDa FGF-2 were transfecte d with a cDNA encoding a dominant negative FGF receptor, alpha 5 beta 1 cell surface levels decreased. Immunoprecipitation of biosynthetical ly labeled cells indicated that expression of 18-kDa FGF-2 increased t he biosynthesis and rate of maturation of alpha 5. Northern blot analy sis showed that 18-kDa FGF-2 increases the level of the alpha 5 subuni t mRNA but does not affect beta 1 subunit transcript levels. Experimen ts utilizing luciferase reporter gene activity revealed increased alph a 5 promoter activity in cells expressing 18-kDa FGF-S indicating that the enhanced alpha 5 transcript level is due to modulation of the tra nscription rate. Therefore, interaction of 18-kDa FGF-2 with FGF recep tors results in changes in alpha 5 beta 1 biosynthesis and processing. In contrast, endogenous expression of HMW FGF-2 does not mediate this effect.