T1 is a c-Fos- and FosB-responsive gene which is induced by growth factors through multiple signal transduction pathways

• Published in: The Journal of biological chemistry 1994-03, Vol.269 (9), p.6866-6873
• Main Authors: KALOUSEK, M. B, TRÜB, T, SCHUERMANN, M, KLEMENZ, R
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Becaplermin; Biological and medical sciences; Blotting, Northern; Blotting, Western; Cell Division - drug effects; Cell Division - physiology; Cell Line; Cycloheximide - pharmacology; Epidermal Growth Factor - pharmacology; Estradiol - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genes, fos; Glycoproteins - biosynthesis; Glycoproteins - isolation & purification; Growth Substances - pharmacology; Insulin - pharmacology; Mice; Mitosis - drug effects; Mitosis - physiology; Molecular and cellular biology; Molecular genetics; Platelet-Derived Growth Factor - pharmacology; Promoter Regions, Genetic; Protein Kinase C - metabolism; Proto-Oncogene Proteins c-fos - biosynthesis; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-sis; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; Signal Transduction - drug effects; Signal Transduction - physiology; Tetradecanoylphorbol Acetate - pharmacology; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation; Transferrin - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)37455-0

Stimulation of quiescent cells with growth factors triggers changes in gene expression through multiple signal transduction pathways. One of these changes in Swiss 3T3 cells is the strong accumulation of T1 mRNA which encodes a secreted glycoprotein of the immunoglobulin superfamily. Proliferating cells continued to express T1 mRNA at a lower level, whereas growth arrest induced either by serum deprivation or by contact inhibition was paralleled by the disappearance of the T1 mRNA. T1 mRNA synthesis in response to serum and platelet-derived growth factor stimulation is mediated through protein kinase C-dependent and protein kinase C-independent pathways. Activation of protein kinase A also led to T1 gene expression. Ongoing protein synthesis is a prerequisite for T1 gene induction by growth factors which defines T1 as a delayed early serum-responsive gene. The ability of the immediate early transcription factors c-Fos and FosB to directly induce the T1 gene was demonstrated in a conditional expression system in the absence of protein synthesis. Furthermore, all known inducers of the T1 gene also lead to c-fos gene activation. Thus we show that the T1 gene is regulated by signals which are transduced through multiple pathways and provide evidence that the Fos proteins play an important role in the integration of these pathways.