Identification of a Phorbol Ester-Repressible v-src-Inducible Gene

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 4; pp. 1178 - 1182
• Main Authors: Simmons, Daniel L., Levy, Daniel B., Yannoni, Yvonne, Erikson, R. L.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-02-1989; National Acad Sciences
• Subjects: 550401 - Genetics- Tracer Techniques; 560300 - Chemicals Metabolism & Toxicology; Amino Acid Sequence; ANIMAL CELLS; ANIMALS; Avian Sarcoma Viruses - genetics; Base Sequence; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BIOLOGICAL EFFECTS; BIRDS; Blotting, Northern; CARCINOGENS; Cells, Cultured; CHEMICAL ACTIVATION; Chick Embryo; CHICKENS; CLONING; Cloning, Molecular; Complementary DNA; CONNECTIVE TISSUE CELLS; DAYS LIVING RADIOISOTOPES; DNA HYBRIDIZATION; DNA SEQUENCING; DNA-CLONING; EMBRYONIC CELLS; ENZYMES; ESTERS; FIBROBLASTS; FOWL; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; GENE REGULATION; GENES; Genes, Viral - drug effects; Genes. Genome; GENETIC EFFECTS; Genetic screening; HYBRIDIZATION; Immediate early genes; ISOTOPES; Kinetics; Libraries; LIGHT NUCLEI; MESSENGER-RNA; MICROORGANISMS; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; MUTANTS; Mutation; NUCLEI; NUCLEIC ACIDS; ODD-ODD NUCLEI; Oncogene Protein pp60(v-src); ONCOGENIC VIRUSES; ORGANIC COMPOUNDS; PARASITES; PC12 cells; PHORBOL ESTERS; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; PHOSPHORUS-GROUP TRANSFERASES; PHOSPHOTRANSFERASES; Protein Kinases - physiology; Proteins; Proto-Oncogenes - drug effects; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIOISOTOPES; Retroviridae Proteins - physiology; RNA; RNA, Messenger - drug effects; RNA, Messenger - genetics; Rous sarcoma virus; SOMATIC CELLS; STRUCTURAL CHEMICAL ANALYSIS; Tetradecanoylphorbol Acetate - pharmacology; Transcription, Genetic - drug effects; TRANSFERASES; VERTEBRATES; VIRUSES; Virus; Oncovirinae; Gene; Induction; Type C oncovirus; Retroviridae; V-Onc gene; Rous sarcoma virus; Primary structure; Identification; Gene expression
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.4.1178

Chicken embryo fibroblasts (CEF) infected with a temperature-sensitive Rous sarcoma virus (RSV) mutant, tsNY72-4, express a set of pp60v-src-induced RNAs soon after shift to the permissive temperature. By subtractive and differential screening, we have cloned 12 of these sequences, 2 of which were c-fos and krox-24. Serum induced all the v-src-inducible genes tested, suggesting that these genes serve roles in normal cell division and are not specific to transformation per se. Significantly, however, v-src produced prolonged, and in some cases kinetically complex, patterns of induction compared to serum. For most of the clones, phorbol 12-tetradecanoate 13-acetate (TPA) induced mRNAs with kinetics similar to that of serum. However, one clone (CEF-4) was expressed in a biphasic manner. Another (CEF-10) was repressed by TPA at 1 hr, after which this mRNA was permanently induced. The pattern of repression-induction of CEF-10 mRNA is the inverse of protein kinase C (PKC) activity in the cell, suggesting that PKC actively represses this gene. In vivo expression of CEF-10 mRNA is restricted predominantly to the lung. A full-length CEF-10 cDNA encodes a 41-kDa protein that has an amino-terminal signal peptide for secretion, contains a markedly high number of cysteine residues, and shows no sequence similarity to known proteins.