Integrin regulation by endogenous expression of 18-kDa fibroblast growth factor-2.
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.
Klein
S
S
Department of Cell Biology, and the Kaplan Cancer Center, New York University Medical Center, New York, New York 10016, USA.
Bikfalvi
A
A
Birkenmeier
T M
TM
Giancotti
F G
FG
Rifkin
D B
DB
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D039482:Integrin alpha5; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D015703:Antigens, CD; D018076:DNA, Complementary; D039482:Integrin alpha5; D019012:Integrin beta1; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2