Human vascular IBP-like growth factor

Details Human vascular IBP-like growth factor Human vascular IBP-like growth factor

1997-09-25

1999-11-30

Ulm, John

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530399, 530402, A61K 3818, C07K 14475

Patent

active

059943025

DESCRIPTION:

BRIEF SUMMARY
This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. The invention also relates to inhibiting the action of such polypeptides.
The polypeptide of the present invention is related to a family of growth regulators comprising cef 10/cyr 61, connective tissue growth factor (CTGF), and nov, as well as the insulin-like growth factor binding protein (IBP) family which modulates the activity of insulin-like growth factor (IGF). The mRNA corresponding to the polypeptide of this invention is highly expressed in vascular cell-types, thus, this polypeptide is hereinafter referred to as human vascular IBP-like growth factor or "VIGF".
Growth factors and other mitogens, including transforming oncogenes, are capable of rapidly inducing a complex set of genes to be expressed by certain cells (Lau, L. F. and Nathans, D., Molecular Aspects of Cellular Regulation, 6:165-202 (1991). These genes, which have been named immediate early or early response genes, are transcriptionally activated within minutes after contact with a growth factor or mitogen, independent of de novo protein synthesis. A group of these immediate early genes encodes secreted, extracellular proteins which are needed for coordination of complex biological processes such as differentiation and proliferation, regeneration and wound healing (Ryseck, R. P. et al, Cell Growth Differ., 2:235-233 (1991).
Highly related proteins which belong to this group include cef 10 from chicken, which was detected after induction by the viral oncogene pp60.sup.v-src (Simmons, D. L. et al, PNAS, U.S.A., 86:1178-1182 (1989). A closely related protein, cyr 61, is rapidly activated by serum or platelet-derived growth factor (PDGF) (O'Brien, T. P. et al, Mol. Cell Biol., 10:3569-3577 (1990). The overall amino acid identity between cef 10 and cyr 61 is as high as 83%. A third member is human connective tissue growth factor (CTGF) (Bradham, D. M. et al., J. Cell. Biol., 114:1285-1294 (1991). CTGF is a cysteine-rich peptide which is secreted by human vascular endothelial cells in high levels after activation with transforming growth factor beta (TGF-.beta.). CTGF exhibits PDGF-like biological and immunological activities and competes with PDGF for a particular cell surface receptor.
A fourth member of the immediate-early proteins is fisp-12, which has been shown to be induced by serum and has been mapped to a region of the murine genome (Ryseck, R. P. et al., Cell Growth Differ., 2:235-233 (1991). Yet another member of this family is the chicken gene, nov, normally arrested in adult kidney cells, which was found to be overexpressed in myeloblastosis-associated virus type 1 induced nephroblastomas. Further, expression of an amino-terminal-truncated nov product in chicken embryo fibroblasts was sufficient to induce transformation (Joliot, V. et al., Mol. Cell. Biol., 12:10-21 (1992).
The expression of these immediate early genes act as "third messengers" in the cascade of events triggered by growth factors. It is also thought that they are needed to integrate and coordinate complex biological processes, such as differentiation and wound healing in which cell proliferation is a common event.
This emerging family of growth regulators is called the CCN family for CTGF; cef 10/cyr 61; and nov. The VIGF polypeptide of the present invention is thought to be a member of this family of growth regulators. The VIGB polypeptide also contains a stretch of cysteines which is highly homologous to insulin-like growth factor (IGF)-binding protein.
At least two different binding proteins have been identified in adult human serum, namely, IGF-binding protein 53 and IGF-binding protein 1. The IGF-binding proteins have both stimulatory and inhibitory effects on IGF. Clemmons, et al, J. Clin. Invest., 77:1548 (1986) showed increased binding to fibroblast and smooth muscle cell surface receptors of IGF in complex with its binding protein. T

REFERENCES:
patent: 5019559 (1991-05-01), Antoniades
Bradham, et al., "Connective Tissue Growth Factor; a Cysteine-rich Mitogen Secreted by Human Vascular Endothelial Cells Is Related to the SRC-induced Immediate Early Gene Product CEF-10", Journal of Cell Biology, vol. 114, No. 6, issued Sep. 1991, pp. 1289-1292.
M. Khorsandi et al. "Effects of Hypophysectomy on Vascular Insulin-Like Growth Factor-1 Gene Expression After Balloon Denudation in Rats", Atherosclerosis, vol. 93, issued 1992, pp. 115-122.
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