Identification of a phorbol ester-repressible v-src-inducible gene.
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.
Simmons
D L
DL
Biological Laboratories, Harvard University, Cambridge, MA 02138.
Levy
D B
DB
Yannoni
Y
Y
Erikson
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects*; D008969:Molecular Sequence Data; D009154:Mutation; D015688:Oncogene Protein pp60(v-src); D011494:Protein Kinases / Q000502:physiology*; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D012191:Retroviridae Proteins / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D012191:Retroviridae Proteins; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D013755:Tetradecanoylphorbol Acetate