Expression of cyr61, a growth factor-inducible immediate-early gene.

Abstract

A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cel growth. We show here that a member of this set of genes, cyr6l (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr6l mRNA is accumulated from the G/G1 transition through mid-Gl. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the GJ/G1 transition and in mid-G1 at the same rate. In logarithmically growing cels, the cyr61 mRNA level is constant throughout the cel cycle. Cyr6l contains an N-terminal secretory signal sequence; however, it is not detected in the culture medium by immunoprecipitation. Cyr6l is synthesized maximaly at 1 to 2 h after serum stimulation and has a short half-life within the cell.

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

“…hCYR61 mRNA was present at relatively high levels in the human heart, lung, skeletal muscle and placenta, and was present at a moderate level in the pancreas and low to undetectable levels in the brain, kidney and liver. These results are consistent with cyr61 expression in the mouse (O'Brien and Lau, 1992;O'Brien et al, 1990). The expression pattern of CTGF was similar to that of hCYR61, except that CTGF mRNA level was high in the kidney where hCYR61 mRNA was undetectable.…”

“…Consistent with its expression pattern in mouse ®broblasts (O'Brien et al, 1990), hCYR61 mRNA was not detected in quiescent human skin ®broblasts, but was abundant in logarithmically growing and serumstimulated cells (Figure 1a). hCYR61 mRNA was superinduced when human skin ®broblasts were stimulated by serum in the presence of cycloheximmide (Figure 1a), con®rming that hCYR61 is an immediate-early gene in human ®broblasts.…”

“…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.…”

“…Both cyr61 (O'Brien et al, 1990;Nathans, 1985, 1987) and ®sp12 (Ryseck et al, 1991) were identi®ed as immediate-early genes, whose transcription is rapidly induced by serum growth factors without requiring de novo protein synthesis (Williams et al, 1992;Herschmann, 1991;Lau and Nathans, 1991). cef10, the chicken ortholog of cyr61, was also cloned as a growth factor-and v-src-inducible immediate-early gene (Simmons et al, 1989).…”

“…Like other immediate-early genes, cyr61 is not expressed in quiescent cells but is rapidly induced upon stimulation by serum, platelet-derived growth factor (PDGF), basic ®broblast growth factor (bFGF; Nathans, 1985, 1987;O'Brien et al, 1990), transforming growth factor-b (Brunner et al, 1991), or the tumor promoter TPA (12-O-tetradecanolyl-phorbol-13-acetate) in tissue culture and in regenerating liver in rodents (Nathans et al, 1988). cyr61 encodes a 40 kDa secreted, heparin-binding protein which associates with the extracellular matrix (ECM) and cell surface (Yang and Lau, 1991).…”