Divalent Cations and Heparin/Heparan Sulfate Cooperate to Control Assembly and Activity of the Fibroblast Growth Factor Receptor Complex

Kan, Mikio; Wang, Fen; Kan, Makiko; To, Bao; Gabriel, Jerome L.; McKeehan, Wallace L.

doi:10.1074/jbc.271.42.26143

Cited by 97 publications

(107 citation statements)

References 43 publications

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“…The importance of this property to biological activity remains to be established. A third model proposes that heparan sulphate molecules bind to both the growth factor and the receptor [78,104,105]. This provides a potential explanation for the finding that stimulation of bFGF binding to receptor requires a minimum heparan sulphate length of 10-12 monomer units [34].…”

Section: Modulation Of Growth-factor-receptor Activationmentioning

confidence: 99%

“…It has been suggested that the extra length is required to generate a bifunctional agent that binds growth factor and receptor simultaneously. Binding of some FGF receptor isoforms to heparan sulphate has been demonstrated [104], although this has been reported to be dependent on high concentrations of magnesium (25 mM) [105]. Additional experimental evidence will be required before this model can be generally accepted.…”

Section: Modulation Of Growth-factor-receptor Activationmentioning

confidence: 99%

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Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

621

497

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This review will summarize our current state of knowledge of the structure, biochemical properties and functions of syndecans, a family of transmembrane heparan sulphate proteoglycans. Syndecans bind a variety of extracellular ligands via their covalently attached heparan sulphate chains. Syndecans have been proposed to play a role in a variety of cellular functions, including cell proliferation and cell–matrix and cell–cell adhesion. Syndecan expression is highly regulated and is cell-type- and developmental-stage-specific. The main function of syndecans appears to be to modulate the ligand-dependent activation of primary signalling receptors at the cell surface. Principal functions of the syndecan core proteins are to target the heparan sulphate chains to the appropriate plasma-membrane compartment and to interact with components of the actin-based cytoskeleton. Several functions of the syndecans, including syndecan oligomerization and actin cytoskeleton association, have been localized to specific structural domains of syndecan core proteins.

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Section: Modulation Of Growth-factor-receptor Activationmentioning

confidence: 99%

Section: Modulation Of Growth-factor-receptor Activationmentioning

confidence: 99%

Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

621

497

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“…For FGFs, HS has been shown to directly facilitate ligand signaling in at least two ways: 1) ligand-HS interaction, which facilitates ligand dimerization (and in turn promotes receptor dimerization) and transactivation (33,34), and 2) receptor-HS interaction, which facilitates ligand-receptor interaction and consequently receptor activation (23,35). As K1 does not bind heparin, we examined whether heparin facilitated K1 signaling through direct and ligand-independent interaction with c-Met.…”

Section: C-met Binds Tightly To Hs Via Its Extracellular Domain-mentioning

confidence: 99%

Dissociation of Heparan Sulfate and Receptor Binding Domains of Hepatocyte Growth Factor Reveals That Heparan Sulfate-c-Met Interaction Facilitates Signaling

Rubin

Day

Breckenridge

et al. 2001

Journal of Biological Chemistry

101

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Hepatocyte growth factor (HGF) is a secreted, heparan sulfate (HS) glycosaminoglycan-binding protein that stimulates mitogenesis, motogenesis, and morphogenesis in a wide array of cellular targets, including hepatocytes and other epithelial cells, melanocytes, endothelial cells, and hematopoietic cells. NK1 is an alternative HGF isoform that consists of the N-terminal (N) and first kringle (K1) domains of full-length HGF and stimulates all major HGF biological activities. Within NK1, the N domain retains the HS binding properties of full-length HGF and mediates HS-stimulated ligand oligomerization but lacks significant mitogenic or motogenic activity. In contrast, K1 does not bind HS, but it stimulates receptor and mitogen-activated protein kinase activation, mitogenesis, and motogenesis, demonstrating that structurally distinct and dissociable domains of HGF are the primary mediators of HS binding and receptor activation. Despite the absence of HS-K1 binding, K1 mitogenic activity in HS-negative cells is strictly dependent on added soluble heparin, whereas K1-stimulated motility is not. We also found that, like the receptors for fibroblast growth factors, the HGF receptor c-Met binds tightly to HS. These data suggest that HS can facilitate HGF signaling through interaction with c-Met that is independent of HGF-HS interaction and that the recruitment of specific intracellular effectors that mediate distinct HGF responses such as mitogenesis and motility is regulated by HS-c-Met interaction at the cell surface.

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“…The involvement of zinc or other metal cations in the binding of heparin to proteins is quite common, although the ions enhancing or inhibiting the reactions differ between systems [33][34][35][36]. The mechanism by which zinc enhances the binding of IL-5 to heparin is unknown.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-5 binds to heparin/heparan sulfate. A model for an interaction with extracellular matrix

Lipscombe

Nakhoul

Sanderson

et al. 1998

Journal of Leukocyte Biology

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Interleukin-5 (IL-5) is the major cytokine regulating eosinophil production. In allergic disease tissue damage is primarily caused by eosinophils. Heparan sulfate proteoglycans are components of the bone marrow stroma, which supports hemopoietic cell differentiation and proliferation. We show that at low IL-5 concentrations heparan sulfate enhances the proliferation of an IL-5-dependent cell line. To investigate a mechanism for this effect we used an artificial proteoglycan to establish an enzyme-linked immunosorbent assay for the binding of heparin to proteins. Using this assay we demonstrate that IL-5 binds to heparin. The IL-5/heparin interaction is inhibited by ethylenediaminetetraacetate and enhanced by low concentrations of zinc ions. IL-5 interacts with iduronic acid containing glycosaminoglycans, and heparan sulfate preparations that have numerous N-sulfated domains per chain are especially efficient at inhibiting heparin binding. Both IL-5/ heparin binding and the synergistic effect of IL-5 and heparan sulfate on cell proliferation were inhibited by an anti-IL-5 monoclonal antibody. These data suggest that the binding of IL-5 to heparan sulfate modulates IL-5 activity.

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Divalent Cations and Heparin/Heparan Sulfate Cooperate to Control Assembly and Activity of the Fibroblast Growth Factor Receptor Complex

Cited by 97 publications

References 43 publications

Syndecans: multifunctional cell-surface co-receptors

Syndecans: multifunctional cell-surface co-receptors

Dissociation of Heparan Sulfate and Receptor Binding Domains of Hepatocyte Growth Factor Reveals That Heparan Sulfate-c-Met Interaction Facilitates Signaling

Interleukin-5 binds to heparin/heparan sulfate. A model for an interaction with extracellular matrix

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