Identification of a phorbol ester-repressible v-src-inducible gene.

Abstract

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.

Human CYR61-mediated enhancement of bFGF-induced DNA synthesis in human umbilical vein endothelial cells

“…These secreted, cysteine-rich proteins have been named members of the`CCN family' (for Cyr61/Cef10, CTGF/Fisp12, and Nov; Bork, 1993) and include at least three distinct members: cyr61/cef10 (Simmons et al, 1989;O'Brien et al, 1990), CTGF/®sp12 (Bradham et al, 1991;Ryseck et al, 1991) and nov Joliot et al, 1992). Members of this protein family share a high level of sequence homology, including complete conservation of 38 cysteine residues in their secreted portion.…”

“…cef10, the chicken ortholog of cyr61, was also cloned as a growth factor-and v-src-inducible immediate-early gene (Simmons et al, 1989). ®sp12 was later found to be the mouse homolog of the human connective tissue growth factor (CTGF; Bradham et al, 1991), which was identi®ed by virtue of its mitogenic activity in human umbilical vein endothelial cells (HUVECs; Bradham et al, 1991).…”

Basic fibroblast growth factor transcriptional autoregulation requires EGR-1

“…Egr-1 is a zinc ®nger transcriptional factor (see Gashler and Sukhatme, 1995) which was also identi®ed as NGFI-A (Milbrandt, 1987), Zif268 (Lau and Nathans, 1987), Cef5 (Simmons et al, 1989), Krox24 (Lemaire et al, 1988) and Tis8 (Lim et al, 1987). Similar to c-Fos, Egr-1 expression is rapidly induced by mitogens such as platelet-derived growth factor (PDGF), FGF and epidermal growth factor (EGF) in ®broblasts (Sukhatme et al, 1987;Lau and Nathans, 1987;Lemaire et al, 1988), suggesting a possible role of Egr-1 in mediating bFGF autoregulation.…”

Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

“…Although CTGF exhibits PDGF-like biological activities and appears to be antigenically related to PDGF, it has little peptide sequence homology to either the PDGF A or B chain peptides. The peptide sequence of CTGF reveals that it is a member of a family of peptides including the v-src-induced CEF-10 peptide identified in src-transformed chicken embryo fibroblasts (Simmons et al, 1989), cyr6l cloned from mouse BALB/ c 3T3 fibroblasts after serum induction (O'Brien et al, 1990), and the serum-induced fispl2 (Ryseck et al, 1991) or TGF-,B-induced BIGM2 transcript identified in 3T3 cells (Brunner et al, 1991). CTGF is also related to the newly described nov gene product that is overexpressed in nephroblastomas induced by myeloblastosisassociated virus (Joliot et al, 1992).…”