Heparin-II Domain of Fibronectin Is a Vascular Endothelial Growth Factor-Binding Domain

Wijelath, Errol S.; Rahman, Salman; Namekata, Mayumi; Murray, Jacqueline; Nishimura, Tomoaki; Mostafavi‐Pour, Zohreh; Patel, Yatin; Suda, Yasuo; Humphries, Martin J.; Sobel, Michael

doi:10.1161/01.res.0000246849.17887.66

Cited by 257 publications

(187 citation statements)

References 39 publications

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“…For instance, FnIII domains in both FN and tenascin-C bind to VEGF, which potentiates the VEGF-mediated signalling through its receptor VEGFR2 (Wijelath et al 2006). FnIII domains of ECM-associated protein anosmin-1 are shown to bind to FGFR1 ectodomains and function as a co-ligand for FGFR1 signal complex, enhancing or inhibiting the activity (Hu et al 2009).…”

Section: Src-fak: the Focal Point For Integrin Signallingmentioning

confidence: 99%

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

Kim

Turnbull²,

Guimond³

2011

Journal of Endocrinology

1,003

816

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Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and proteoglycans. ECM provides the bulk, shape and strength of many tissues in vivo, such as basement membrane, bone and cartilage. In vitro, most animal cells can only grow when they are attached to surfaces through ECM. ECM is also the substrate for cell migration. However, ECM provides much more than just mechanical and structural support, with implications in developmental patterning, stem cell niches and cancer. ECM imparts spatial context for signalling events by various cell surface growth factor receptors and adhesion molecules such as integrins. The external physical properties of ECM may also have a role in the signalling process. ECM molecules can be flexible and extendable, and mechanical tension can expose cryptic sites, which could further interact with growth factors or their receptors. ECM proteins and structures can determine the cell behaviour, polarity, migration, differentiation, proliferation and survival by communicating with the intracellular cytoskeleton and transmission of growth factor signals. Integrins and proteoglycans are the major ECM adhesion receptors which cooperate in signalling events, determining the signalling outcomes, and thus the cell fate. This review focuses on the emerging concept of spatial cell biology of ECM, especially the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.

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Section: Src-fak: the Focal Point For Integrin Signallingmentioning

confidence: 99%

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

Kim

Turnbull²,

Guimond³

2011

Journal of Endocrinology

1,003

816

View full text Add to dashboard Cite

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“…Recently vascular endothelial growth factor (VEGF), a member of the PDGF/VEGF family of growth factors, was shown to bind directly to fibronectin (14)(15)(16)(17). This binding was significantly enhanced by heparin (14,15,18), which acts by modifying the structure of fibronectin, potentially revealing previously masked VEGF binding sites that remain available to bind VEGF even after heparin is removed (14).…”

mentioning

confidence: 99%

PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation

Smith

Mitsi

Nugent

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Platelet-derived growth factor (PDGF) signaling is essential for processes involving cell motility and differentiation during embryonic development in a wide variety of organisms including the mouse, frog, zebrafish, and sea urchin. In early Xenopus laevis embryos, PDGF-AA provides guidance cues for the migration of anterior mesendoderm cells as they move across a fibronectin-rich extracellular matrix. The long form of PDGF-A includes a positively charged carboxyl-terminal retention motif that can interact with the extracellular matrix and heparan sulfate proteoglycans (HSPGs). In this study we demonstrate that PDGF-AA binds directly to fibronectin and that this association is greatly enhanced by heparin. The PDGF-AA-fibronectin binding occurs across a broad range of pHs (5.5-9), which is significant because the PDGF-guided migration of Xenopus mesendoderm cells occurs under basic extracellular conditions (pH 8.4). We further demonstrate that endogenous HSPG's are required for the PDGF-AA-guided mesendoderm movement, suggesting an in vivo role for HSPGs in mediating the interaction between PDGF-AA and fibronectin.embryo ͉ embryonic development ͉ mesendoderm ͉ mesoderm

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“…In fact, vascular endothelial growth factor has recently been shown to bind specific sites on FN, suggesting potential sequestration in more basic reconstituted systems. Thus, ECM protein-mediated sequestration may play a role in diminishing GF-mediated signaling on FN-coated dishes, especially in systems employing low doses of GF (42). In fact, because NIH-3T3 cells deposit their own matrix, it remains a possibility that ECM proteins other than the adsorbed FN may be responsible for the observed desensitization, possibly via GF sequestration.…”

Section: Discussionmentioning

confidence: 99%

Selective Desensitization of Growth Factor Signaling by Cell Adhesion to Fibronectin

Galownia

Kushiro

Gong

et al. 2007

Journal of Biological Chemistry

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Cell adhesion to the extracellular matrix is required to execute growth factor (GF)-mediated cell behaviors, such as proliferation. A major underlying mechanism is that cell adhesion enhances GF-mediated intracellular signals, such as extracellular signal-regulated kinase (Erk). However, because GFs use distinct mechanisms to activate Ras-Erk signaling, it is unclear whether adhesion-mediated enhancement of Erk signaling is universal to all GFs. We examined this issue by quantifying the dynamics of Erk signaling induced by epidermal growth factor, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) in NIH-3T3 fibroblasts. Adhesion to fibronectin-coated surfaces enhances Erk signaling elicited by epidermal growth factor but not by bFGF or PDGF. Unexpectedly, adhesion is not always a positive influence on GF-mediated signaling. At critical subsaturating doses of PDGF or bFGF, cell adhesion ablates Erk signaling; that is, adhesion desensitizes the cell to GF stimulation, rendering the signaling pathway unresponsive to GF. Interestingly, the timing of growth factor stimulation proved critical to the desensitization process. Erk activation significantly improved only when pre-exposure to adhesion was completely eliminated; thus, concurrent stimulation by GF and adhesion was able to partially rescue adhesionmediated desensitization of PDGF-and bFGF-mediated Erk and Akt signaling. These findings suggest that adhesion-mediated desensitization occurs with rapid kinetics and targets a regulatory point upstream of Ras and proximal to GF receptor activation. Thus, adhesion-dependent Erk signaling is not universal to all GFs but, rather, is GF-specific with quantitative features that depend strongly on the dose and timing of GF exposure.

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Heparin-II Domain of Fibronectin Is a Vascular Endothelial Growth Factor-Binding Domain

Cited by 257 publications

References 39 publications

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation

Selective Desensitization of Growth Factor Signaling by Cell Adhesion to Fibronectin

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