Morphological characterization of membrane systems in A- and B-cells of the Chinese hamster

Orci, Lelio; Amherdt, M; Malaisse‐Lagae, Francine; Perrelet, Alain; We, Dulin; Gc, Gerritsen; Wj, Malassie; Ae, Renold

doi:10.1007/bf01221983

Cited by 18 publications

(11 citation statements)

References 6 publications

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“…Although insulin in solution at concentrations at which it induces most of its biological responses is monomeric and presumably "monovalent," these observations, together with the previous findings that insulin receptors are mobile (28) or clustered (25,26), suggested a possible role for receptor aggregation or crosslinking in the action of insulin itself. To explore this possibility, we exposed cells to a submaximal dose of insulin and then to low concentrations of anti-insulin antibody (about 0.5-1.0 mol of antibody per mol of insulin).…”

Section: Resultsmentioning

confidence: 65%

“…Almost no clues exist as to the nature of the transmembrane signal itself. A possible role for movement of receptors in the plane of the membrane has been suggested by the finding that insulin receptors appear to be clustered (25,26), and a temperature-dependent delay in the onset of insulin action has been noted (27). Using fluorescent derivatives of insulin, Schlessinger et al (28) have shown that insulin on fibroblasts can move laterally with a diffusion coefficient (3-5 X 10-10 cm2/sec) similar to that for other mobile membrane proteins.…”

Section: Resultsmentioning

confidence: 99%

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Direct demonstration that receptor crosslinking or aggregation is important in insulin action

Kahn

Baird

Jarrett

et al. 1978

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

348

124

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Exposure of adipocytes to antibodies to the insulin receptor results in a blockade of 125I-labeled insulin binding, stimulation of glucose oxidation, and many more insulin-like effects. Allowing for differences in purity, antireceptor antibody is equipotent with insulin on a molar basis. Both the bivalent F(ab')2 and monovalent Fab' fragments of the antireceptor antibody are fully active in inhibiting 25I-labeled insulin binding. Bivalent F(ab')% also retains its insulin-like effects.

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Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Direct demonstration that receptor crosslinking or aggregation is important in insulin action

Kahn

Baird

Jarrett

et al. 1978

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

348

124

View full text Add to dashboard Cite

show abstract

“…Recent electron microscope studies of biologically active ferritin-labeled insulin by L. Jarett and co-workers in St. Louis, Mo. (58) and L. Orci and co-workers in Geneva (59), have directly demonstrated the occurrence of both dispersed and "clustered" distribution of insulin receptors on the membrane of fat cells (Fig. 8) and liver (Fig.…”

Section: Conclusion: New Models Of Hormone Binding and Actionmentioning

confidence: 96%

Cooperative properties of hormone receptors in cell membranes

Meyts

1976

J Supramol Struct

164

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The binding of many polypeptide hormones to cell surface receptors does not appear to follow the law of mass action. While steady-state binding data are consistent in many cases with either heterogeneous populations of binding sites or interactions of the type known as negative cooperativity, study of the kinetics of dissociation of the type known as negative cooperativity, study of the kinetics of dissociation of the hormone receptor complex allows an unambiguous demonstration of cooperative interactions. Negative cooperativity, which seems to be wide-spread among hormone receptors, provides exquisite sensitivity of the cell at low hormone concentrations while buffering against acutely elevated hormone levels. The molecular mechanisms underlying the cooperativity are still largely unknown. Cooperativity may stem from a conformational transition in individual receptors or involve receptor aggregation in the fluid membrane (clustering) or more extensive membrane phenomena. Thus, new models of hormone action must be considered which integrate the progress in our knowledge of both the complex mechanisms regulating hormone binding to their surface receptors, and the dynamic properties of the cell membrane.

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“…Unless the bioactive EGF-receptor complex retained at the plasma membrane is covalently linked it is difficult to see how it escapes the normal internalization pathway; possibly the complexes are compartmentalized in some way which prevents them from being swept into the degradation sequence. (For example, Orci et al (69) have observed the presence of intramembranous insulin receptor complexes using freeze fracture techniques; such complexes may be a class distinct from those destined for degradation.) It is possible that a major class of low affinity EGF receptors either are or subsequently become attached in some way to a cytoskeletal system when EGF binds and thereafter are destined for internalization and degradation.…”

Section: Kinetics Of Egf Bindingmentioning

confidence: 97%

Epidermal growth factor receptors

1981

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EGF-Rs are cell membrane glycoproteins of wide distribution. They have not yet been fully characterized or purified but are probably molecules of 170-190,000 mol. wt. in most cells. The growth factor EGF binds and will saturate cell surface receptors with a KA of about 5 X 10(9) M-1 although a receptor class with an affinity in excess of 10(10) M-1 has been detected in some cells. The number of receptors on a cell does not determine the level of its response. Some cell types have receptors which bind EGF, but with no mitogenic response. The ways in which receptor affinity and/or number is modulated are described. This and other evidence is reviewed in a search for a suitable model of a mechanism of action on the cell, which best fits the current data. There is ample evidence that EGF binds to the receptor; that ligand-receptor complexes cluster or aggregate; and then are internalized and degraded, but evidence for a direct connection between internalization and the subsequent mitogenic response is lacking. Good correlations between internalization and mitogenic responses have been observed and developed into a theory of endocytic activation, but there is a body of evidence which cannot be accommodated by this theory. Instead, an alternative model is suggested.

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Morphological characterization of membrane systems in A- and B-cells of the Chinese hamster

Cited by 18 publications

References 6 publications

Direct demonstration that receptor crosslinking or aggregation is important in insulin action

Direct demonstration that receptor crosslinking or aggregation is important in insulin action

Cooperative properties of hormone receptors in cell membranes

Epidermal growth factor receptors

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