Ganglioside GM3 is stably associated to tyrosine-phosphorylated ErbB2/EGFR receptor complexes and EGFR monomers, but not to ErbB2

Milani, S.; Sottocornola, E.; Zava, Stefania; Berselli, Patrizia; Berra, B.; Colombo, Irma

doi:10.1016/j.bbalip.2007.04.008

Cited by 9 publications

(4 citation statements)

References 38 publications

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“…Ganglioside regulation of ERBB receptors activity is crucially dependent on the number of gangliosides actually residing in microdomains ( Figure 2 ). Several studies have provided information on the role of GM3 in the localization of ERBB receptors in relation to their phosphorylation [ 125 , 126 , 127 , 128 ]. Very recently, it has been reported that disialogangliosides, such as GD3 and GD2, enhance EGFR signaling, resulting in the expression of a cancer stem cell phenotype and a reduced sensitivity to Gefitinib [ 86 ].…”

Section: How Glycosylation Modulates the Activity Of Specific Recementioning

confidence: 99%

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Ferreira¹,

Pucci

Venturi

et al. 2018

IJMS

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Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1) by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2) through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3) by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

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Section: How Glycosylation Modulates the Activity Of Specific Recementioning

confidence: 99%

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Ferreira¹,

Pucci

Venturi

et al. 2018

IJMS

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“…A large body of data points to the interaction between GM3 and the ERBB membrane receptors family [216]. GM3 interacts with the GlcNAc termini of N-linked chains of ERBB1 (EGF receptor, EGFR), inhibiting its ligand-dependent activation [217][218][219][220], while the interaction of GM3 with the EGFR/ ERBB2 heterodimer induces its retention in lipid rafts in a phosphorylated form [221][222][223]. The expression of ST3GAL5 and of GM3 in non small cell lung cancer results in an increased number of EGFR molecules and increased sensitivity to the EGFR-tyrosine kinase gefitinib [224].…”

Section: How the Expression Of Sialylated Glycans On The Cell Membranmentioning

confidence: 99%

Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression

Dall’Olio

Malagolini

Trinchera

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

101

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“…Early observations demonstrated an inhibitory action of specific gangliosides on cell growth, and suggested that gangliosides modulate receptors [80]. Later work suggested that the ganglioside GM3 directly interacted with N-linked sugars on the extracellular domain of the activated EGF receptor to inhibit its receptor tyrosine kinase activity [81][82][83], and that GM3 induced the receptor's presence in detergent-resistant membranes, suggesting a change in the organization of the receptor and its coreceptor ErbB2 on the cell surface [84]. Similar interactions have been described for other receptors, like the insulin receptor [85] and for integrins, in which case GM3 and GM2 mediated the interaction of the integrins with other proteins [75].…”

Section: Glycosphingolipids and Their Trans-and Cis-interactionsmentioning

confidence: 99%

Sphingolipid topology and the dynamic organization and function of membrane proteins

Meer¹,

Hoetzl²

2009

FEBS Letters

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a b s t r a c tWhen acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi then allowed them to create membranes of different lipid composition, notably a thin, flexible ER membrane, consisting of glycerolipids, and a sturdy plasma membrane containing at least 50% sphingolipids and sterols. Besides sorting membrane proteins, in the course of evolution the simple sphingolipids obtained key positions in cellular physiology by developing specific interactions with (membrane) proteins involved in the execution and control of signaling. The few signaling sphingolipids in mammals must provide basic transmission principles that evolution has built upon for organizing the specific regulatory pathways tuned to the needs of the different cell types in the body.

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Ganglioside GM3 is stably associated to tyrosine-phosphorylated ErbB2/EGFR receptor complexes and EGFR monomers, but not to ErbB2

Cited by 9 publications

References 38 publications

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression

Sphingolipid topology and the dynamic organization and function of membrane proteins

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