FGF-2, BMP-2, and BMP-4 regulate retinoid binding proteins and receptors in 3T3 cells.
An Important part of intercellular signalling is the ability of responding cells to regulate multiple signal transduction pathways. Just as retinoic acid exposure alters expression of many peptide growth factors and their receptors, we have found that peptide growth factors alter the expression of cellular retinoic acid binding proteins (CRABPs) and retinoic acid receptors (RARs). FGF-2 (basic fibroblast growth factor) treatment of BALB 3T3 fibroblasts increased the level of CRABP I RNA, whereas bone morphogenetic protein (BMP)-2 and BMP-4 reduced this level as well as the levels of CRABP II and RAR beta 1/beta 3 transcripts. Regulation of the CRABP I gene by FGF-2 occurred posttranscriptionally by increasing RNA stability. However, BMP-2 down-regulated CRABP I message without affecting message stability. Neither of these mechanisms was dominant, with intermediate levels of CRABP I RNA occurring in the presence of both FGF-2 and BMP-2 or BMP-4. These two different modes of regulation thus allow different levels of CRABP I RNA accumulation in the presence of different ratios of FGF-2 and BMP-2 or BMP-4.
Means
A L
AL
Department of Pharmacology, Cornell University Medical College, New York, New York 10021, USA.
Gudas
L J
LJ
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002453:Cell Cycle; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051379:Mice; D012313:RNA / Q000032:analysis / Q000037:antagonists & inhibitors; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018168:Receptors, Retinoic Acid; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D012313:RNA