EPIDERMAL GROWTH-FACTOR ACTIVATION OF VINCULIN AND BETA-1-INTEGRIN GENE-TRANSCRIPTION IN QUIESCENT SWISS 3T3 CELLS - REGULATION THROUGH A PROTEIN-KINASE C-INDEPENDENT PATHWAY

被引:0
作者
BELLAS, RE
BENDORI, R
FARMER, SR
机构
[1] BOSTON UNIV,SCH MED,DEPT BIOCHEM,80 E CONCORD ST,BOSTON,MA 02118
[2] WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL
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中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Growth activation of quiescent Swiss 3T3 fibroblasts leads to a rapid induction of vinculin and beta-1-integrin gene expression. Addition of serum, epidermal growth factor (EGF), or platelet-derived growth factor to serum-starved, density-arrested cells resulted in a rapid increase in vinculin and beta-1-integrin mRNA levels and a corresponding increase in vinculin synthesis. The increase in vinculin and beta-1-integrin mRNA expression by serum or EGF was not blocked by the inhibition of protein synthesis by cycloheximide. The kinetics of induction of vinculin and beta-1-integrin mRNAs by EGF are different: vinculin mRNA levels reached a peak of expression 4-5-fold greater than that measured in quiescent cells by 2 h after addition of growth factor, whereas beta-1-integrin mRNA levels increased more slowly and to a lesser extent, reaching peaks of 2-3-fold induction at 5 h poststimulation. Down-regulation of protein kinase C by prolonged pretreatment of cells with phorbol 1,2-myristate 1,3-acetate had no effect on the ability of EGF or platelet-derived growth factor to activate vinculin or beta-1-integrin mRNA expression. Furthermore, direct activation of protein kinase C with 1,2-myristate 1,3-acetate did not induce the expression of vinculin or beta-1-integrin mRNA, but did activate c-fos expression. In vitro nuclear "run-on" transcription assays demonstrate a greater than 7-fold increase in vinculin and beta-1-integrin transcription at 40-60 min after addition of EGF when compared with levels in quiescent cells. This activation was rapid and transient, but appeared to occur later than the increase in c-fos and actin transcription. These results demonstrate that vinculin and beta-1-integrin, important components of the cell adhesion apparatus, are members of a group of immediate early growth-responsive genes, along with c-fos, c-myc, actin, and fibronectin. In addition, regulation of these cell adhesion genes occurs exclusively through a protein kinase C-independent pathway in serum-deprived, density-arrested Swiss 3T3 cells.
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页码:12008 / 12014
页数:7
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