Glycosylation of the epidermal growth factor receptor in A-431 cells. The contribution of carbohydrate to receptor function.

Soderquist, Ann Mangelsdorf; Carpenter, Graham

doi:10.1016/s0021-9258(18)90787-8

Cited by 211 publications

(19 citation statements)

References 39 publications

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“…A stringent requirement for N-linked glycosylation has also been shown for the basic fibroblast growth factor receptor (30). Moreover, at least partial glycosylation of the receptors for the epidermal growth factor (31) or insulin (32) was necessary to acquire ligandbinding capacity. On the other hand, inhibition of N-linked glycosylation or deglycosylation of LH receptors (33) or ␤-adrenergic receptors (34) did not influence ligand-binding properties.…”

Section: Discussionmentioning

confidence: 98%

Molecular Characterization and Functional Analysis of Murine Interleukin 4 Receptor Allotypes

Schulte

Kurrle

Röllinghoff

et al. 1997

The Journal of Experimental Medicine

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The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or as soluble (s)IL-4–binding molecule with potent immunoregulatory effects. In this study we identified and characterized a murine IL-4R allotype. Sequence analysis of the IL-4R cDNA of BALB/c mice revealed 18 base substitutions leading to three extracellular and five cytoplasmic amino acid changes when compared with the published IL-4R sequence of C57BL/6 mice. Analyses with allotype-specific mAbs revealed that AKR/J and SJL/J mice possess the newly identified BALB/c IL-4R allotype whereas the IL-4Rs of C3H, CBA, DBA-2, and FVB/N mice are identical to that of the C57BL/6 mouse. The extracellular Thr49 to Ile substitution abrogates one N-glycosylation site in the naturally occurring BALB/c IL-4R as well as in the experimentally point mutated C57BL/6-T49I sIL-4R, and both molecules display a nearly threefold reduction in IL-4–neutralizing activity compared to the C57BL/6 sIL-4R. In line with this, a significantly enhanced dissociation rate of IL-4 was detected for the BALB/c IL-4R allotype by surface plasmon resonance and in radioligand binding studies with IL-4R–transfected cell lines. These findings suggest that the altered ligand binding behavior of the newly described IL-4R allotype may influence the IL-4 responsiveness, thus contributing to the diverse phenotypes of inbred mouse strains in IL-4–dependent diseases.

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Section: Discussionmentioning

confidence: 98%

Molecular Characterization and Functional Analysis of Murine Interleukin 4 Receptor Allotypes

Schulte

Kurrle

Röllinghoff

et al. 1997

The Journal of Experimental Medicine

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“…Membrane-bound receptors for hormones and growth factors are generally glycosylated. Of particular interest is the conservation of consensus sequences for N-glycosylation among Partial glycosylation is required for processing and\or hormonebinding activity of insulin receptor [34,35], epidermal-growthfactor receptor [36,37], nicotinic acetylcholine receptor [38], and members of the G-protein-coupled class of receptors, including the vasoactive intestinal peptide receptor [39], somatostatin receptor [40] and β-adrenergic receptor [41,42]. The main purpose of the present study was to verify the role of N-glycosylation in the cell-surface expression and the ligand-binding properties of the AT # receptor.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the role of N-glycosylation in cell-surface expression and binding properties of angiotensin II type-2 receptor of rat pheochromocytoma cells

Servant

Dudley²,

Escher

et al. 1996

Biochemical Journal

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We previously demonstrated that the AT2 receptor is a glycoprotein containing N-linked oligosaccharide side chains and that the marked disparity between the sizes of AT2 receptors from different tissues was related to different degrees of N-glycosylation. In the present study, we used an inhibitor of N-glycosylation, tunicamycin, as well as an endoglycosidase, glycopeptidase-F, to examine the contribution of carbohydrate moieties to the ligand-binding properties, cell-surface expression and apparent molecular mass of AT2 receptors of rat pheochromocytoma cells (PC-12 cells). Photoaffinity labelling of cell-surface AT2 receptors revealed that PC-12 cells grown in the presence of tunicamycin expressed, in addition to the previously described 140 kDa receptor, lower-molecular-mass receptors of 63 kDa, 47 kDa and 32 kDa. Lectin affinity chromatography revealed that the 63 kDa and the 47 kDa receptors are partially glycosylated and that the 32 kDa receptor is completely deglycosylated. Competitive binding experiments were carried out on tunicamycin-treated cells that expressed predominantly the 63 kDa or the 47 kDa receptors. Both receptor forms exhibited a high affinity for angiotensin II, although a slight decrease (of about 2-fold) was consistently observed on tunicamycin-treated cells as compared with control cells. Endoglycosidase digestion of AT2 receptors of PC-12 cells also yielded smaller receptor forms of 47 kDa and 32 kDa. Similarly, angiotensin II showed a high but slightly decreased binding affinity (of about 2-fold) for deglycosylated membranes as compared with control membranes. In conclusion, the stepwise action of tunicamycin suggests the presence of at least three N-linked oligosaccharide side chains on the AT2 receptor of PC-12 cells. These oligosaccharide side chains have a minor contribution to the affinity of the receptor. Interestingly, glycosylation is not an essential requirement for the expression of AT2 receptor at the surface of PC-12 cells.

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“…In the case of the EGF receptor studied in A-431 cells, monensin treatment resulted in an immature form of the receptor that was detected at the cell surface and exhibited EGF binding and EGF-dependent autophosphorylation (Soderquist and Carpenter, 1984). However, it is not known if ligand binding to this immature form of the EGF receptor can lead to autocrine signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Autocrine stimulation by the v-sis gene product requires a ligand-receptor interaction at the cell surface.

Hannink

Donoghue

1988

The Journal of Cell Biology

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Abstract. Autocrine expression of a growth factor and its receptor in the same cell raises the possibility of an intracellular receptor-ligand interaction within the cell, in addition to a receptor-ligand interaction at the cell surface. We have constructed a NIH3T3 cell line which contains the v-sis gene under the inducible control of the Drosophila melanogaster hsp70 promoter. Expression of both v-sis RNA and protein is rapidly induced by a short period of heat-shock. We have ana- tor that occurs at the cell surface, rather than an intracellular location. THE intrinsic relationship between malignant transformation and normal cellular growth factors is now well established. This relationship is explicitly described in the autocrine model of transformation in which the continued proliferation of a cell is dependent upon synthesis of a growth factor by the same cell. This model was first advanced to account for the production of transforming growth factors (TGFs) t by murine sarcoma virus-transformed cells (DeLarco and Todaro, 1978;Sporn and Todaro, 1980). The subsequent discovery that simian sarcoma virus (SSV) encodes a protein homologous to the B chain of platelet-derived growth factor (PDGF-B) provided strong evidence for the role of autocrine growth factors in transformation (Waterfield et al., 1983;Doolittle et al., 1983).The central feature of the autocrine model is the coexpression in the same cell of a growth factor and its receptor. The cellular location of the receptor-ligand interaction is an important question. All growth factors and their receptors are synthesized on membrane-bound polysomes and translocated into the lumen of the rough endoplasmic reticulum as nascent polypeptide chains. From the RER, growth factors Mark Hannink's present address is McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706.1. Abbreviations used in this paper: EGF, epidermal growth factor; GM-CSF, granulocyte macrophage colony-stimulating factor; PDGE plateletderived growth factor; SSV, simian sarcoma virus; TGF, transforming growth factor. and their receptors are transported to the cell surface through the Golgi stacks and secretory vesicles (Farquhar, 1985). Although the signals that direct the transport of proteins through the Golgi and secretory vesicles to the cell surface are not well understood, it is likely that growth factors and their receptors use the same mechanism for cell surface transport and presumably are present within the same membrane vesicles during transport (Goding, 1982;Strous et al., 1983).The availability of cDNA clones encoding various growth factor molecules has allowed direct testing of the autocrine model. Expression of a cDNA encoding human TGF-alpha (Rosenthal et al., 1986), or a synthetic gene encoding human epidermal growth factor (EGF) (Stern et al., 1987) in Rat-1 fibroblasts results in anchorage-independent growth and tumor formation. However, expression of human TGF-alpha was not sufficient to transform NIH3T3 cells (Finzi et al., 1987), indicative...

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Glycosylation of the epidermal growth factor receptor in A-431 cells. The contribution of carbohydrate to receptor function.

Cited by 211 publications

References 39 publications

Molecular Characterization and Functional Analysis of Murine Interleukin 4 Receptor Allotypes

Molecular Characterization and Functional Analysis of Murine Interleukin 4 Receptor Allotypes

Analysis of the role of N-glycosylation in cell-surface expression and binding properties of angiotensin II type-2 receptor of rat pheochromocytoma cells

Autocrine stimulation by the v-sis gene product requires a ligand-receptor interaction at the cell surface.

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