Cyr61, a Product of a Growth Factor-Inducible Immediate-Early Gene, Promotes Cell Proliferation, Migration, and Adhesion
Open accessAbstract
cyr61 was first identified as a growth factor-inducible immediate-early gene in mouse fibroblasts. The encoded Cyr61 protein is a secreted, cystein-rich heparin-binding protein that associates with the cell surface and the extracellular matrix, and in these aspects it resembles the Wnt-1 protein and a number of known growth factors. During embryogenesis, cyr61 is expressed most notably in mesenchymal cells that are differentiating into chondrocytes and in the vessel walls of the developing circulatory system. cyr61 is a member of an emerging gene family that encodes growth regulators, including the connective tissue growth factor and an avian proto-oncoprotein, Nov cyr61 also shares sequence similarities with two Drosophila genes, twisted gastrulation and short gastrulation, which interact with decapentaplegic to regulate dorsal-ventral patterning. In this report we describe the purification of the Cyr61 protein in a biologically active form, and we show that purified Cyr61 has the following activities: (i) it promotes the attachment and spreading of endothelial cells in a manner similar to that of fibronectin; (ii) it enhances the effects of basic fibroblast growth factor and platelet-derived growth factor on the rate of DNA synthesis of fibroblasts and vascular endothelial cells, although it has no detectable mitogenic activity by itself; and (iii) it acts as a chemotactic factor for fibroblasts. Taken together, these activities indicate that Cyr61 is likely to function as an extracellular matrix signaling molecule rather than as a classical growth factor and may regulate processes of cell proliferation, migration, adhesion, and differentiation during development.
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CCN1 is tightly associated with the ECM after secretion and supports cell adhesion by directly binding integrin receptors.
“early studies on CCN1 showed that it is tightly associated with the ECM upon secretion [13] and supports cell adhesion through direct binding to integrin receptors [14,15]”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [14]
CCN1 does not induce cell proliferation by itself but only enhances DNA synthesis induced by other mitogens.
“CCN1 does not induce cell proliferation on its own but only enhances DNA synthesis induced by other mitogens [14]”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [14]
CCN1 does not induce DNA synthesis alone but synergizes with other mitogenic growth factors to augment growth factor-induced DNA synthesis in fibroblasts and endothelial cells through integrin αvβ3.
“Although CCN1 does not induce DNA synthesis on its own, it can synergize with other mitogenic growth factors to augment growth factor-induced DNA synthesis in both fibroblasts and endothelial cells through integrin αvβ3 [14,71].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [14]
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Retracted
- Authors
- Kireeva, M. L., Mo, F.-E., Yang, G. P., & Lau, L. F.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1996-04
- Volume
- 16
- Issue
- 4
- Pages
- 1326-1334
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC231116
- OpenAlex
- W1925481732
- Cited by
- 341
- References
- 50
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 10 · 2018: 4 · 2017: 5 · 2016: 15 · 2015: 12 · 2014: 12 · 2013: 11 · 2012: 10
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Cancer Institute (R01 CA46565-08, R01CA046565)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- CYR61, connective tissue growth factor, immediate early genes, heparin-binding protein, extracellular matrix signaling, cell adhesion, cell migration, cell proliferation, endothelial cell adhesion, basic fibroblast growth factor, platelet-derived growth factor, chemotaxis, fibroblast differentiation, chondrogenic differentiation, twisted gastrulation, short gastrulation, decapentaplegic, dorsoventral patterning, embryonic development
- MeSH terms
- Animals, Cell Adhesion, Cell Division, Cell Movement, Chemotaxis, DNA, Growth Substances, Heparin, Recombinant Proteins, 3T3 Cells, Genes, Immediate-Early, Immediate-Early Proteins, Intercellular Signaling Peptides and Proteins, Mice, Cysteine-Rich Protein 61
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