Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation

Spivak-Kroizman, Taly R.; Lemmon, Mark A.; Đikić, Ivan; Ladbury, John E.; Pinchasi, Dalia; Huang, Jing-Zhi; Jaye, Michael; Crumley, Gregg; Schlessinger, Joseph; Lax, Irit

doi:10.1016/0092-8674(94)90032-9

Cited by 676 publications

(487 citation statements)

References 38 publications

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“…Binding of heregulin to two di erent members of the RTK I family, speci®cally HER-3 , and HER-4 (Plowman et al, 1993), as well as the documented interactions between these receptors and EGFR (Prigent and Lemoine, 1992;Karunagaran et al, 1995Karunagaran et al, , 1996Pinkas-Kramarski et al, 1996;Riese et al, 1995;Spivak-Kroizman et al, 1992;Qian et al, 1994;Alimandi et al, 1997), suggests that complex combinations of receptor-ligand interactions are occurring in human cells expressing these receptors. Additionally, binding of EGF to HER-2/HER-3 heterodimers occurs (Alimandi et al, 1997), indicating that competition between HRG and EGF for binding to this receptor combination might occur in vivo.…”

Section: Discussionmentioning

confidence: 99%

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Akita²,

et al. 1999

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The heregulins are a family of ligands with ability to induce phosphorylation of the p185 HER-2/neu receptor. Various investigators have reported a variety of responses of mouse and human breast and ovarian cells to this family of ligands including growth stimulation, growth inhibition, apoptosis and induction of di erentiation in cells expressing the HER-2/neu receptor. Some of the disparity in the literature has been attributed to variations in the cell lines studied, ligand dose applied, methodologies utilized or model system evaluated (i.e. in vitro or in vivo). To evaluate the e ects of heregulin on normal and malignant human breast and ovarian epithelial cells expressing known levels of the HER-2/ neu receptor, this report presents the use of several di erent assays, performed both in vitro and in vivo, in vitro proliferation assays, direct cell counts, clonogenicity under anchorage-dependent and anchorage-independent conditions, as well as the in vivo e ects of heregulin on human cells growing in nude mice to address heregulin activity. Using a total of ®ve di erent biologic assays in nine di erent cell lines, across two di erent epithelia and over a one log heregulin dose range, we obtained results that clearly indicate a growth-stimulatory role for this ligand in human breast and ovarian epithelial cells. We ®nd no evidence that heregulin has any growth-inhibitory e ects in human epithelial cells. We also quantitated the amount of each member of the type I receptor tyrosine kinase family (RTK I, i.e. HER-1, HER-2, HER-3 and HER-4) in the cell lines employed and correlated this to their respective heregulin responses. These data demonstrate that HER-2/neu overexpression itself a ects the expression of other RTK I members and that cells expressing the highest levels of HER-2/neu have the greatest response to HRG.

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Section: Discussionmentioning

confidence: 99%

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Akita²,

et al. 1999

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“…The best characterized HS-dependent growth factors are FGF-1 and FGF-2, but other FGFs, HB-EGF, wingless (a member of the Wnt family) and probably several other growth factors belong to this group (Rapraeger et al, 1991;Yayon et al, 1991;Aviezer and Yayon, 1994;Tessler et al, 1994;Zioncheck et al, 1995;Reichsman et al, 1996). Models that have been put forth to explain HS-dependence include ones in which binding of HS to growth factor, receptor, or both directly alters affinity (e.g., through cross-linking, dimerization, or induction of a conformational change [Kan et al, 1993;Pantoliano et al, 1994;Spivak-Kroizman et al, 1994]). Thus, HS dependence is thought to reflect a contribution of HSPGs to binding affinity, i.e., to the thermodynamics of binding.…”

Section: Rotes Of Pgs In Growth Factor Signatingmentioning

confidence: 99%

Proteoglycans: Master regulators of molecular encounter?

Lander

1998

Matrix Biology

103

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“…One or both of the sugars contain one or two sulfate residues. Thus each GAG chain bears many negative charges, which makes it possible for proteoglycans to bind various positively charged molecules such as certain growth factors, cytokines, and chemokines [12]. Proteoglycans are usually named according to the structure of their principal repeating disaccharide of the attached GAG chains, which usually are added to the core proteins at serine residues through a sugar linker.…”

Section: Introductionmentioning

confidence: 99%

The interaction of versican with its binding partners

et al. 2005

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Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix (ECM). Versican, like other members of its family, has unique N-and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type I collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P-and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.

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Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation

Cited by 676 publications

References 38 publications

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Proteoglycans: Master regulators of molecular encounter?

The interaction of versican with its binding partners

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