Proximity measurements between H-2 antigens and the insulin receptor by fluorescence energy transfer: evidence that a close association does not influence insulin binding.

Liegler, Teri; Szöllősi, János; Hyun, William C.; Goodenow, Robert S.

doi:10.1073/pnas.88.15.6755

Cited by 28 publications

(24 citation statements)

References 42 publications

(35 reference statements)

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“…To better define a specific signal in mAb IV.3-labeled cells, further gating on the list mode data was made to select the brightest 10% of cells. After correction for autofluorescence and spectral overlap, energy transfer efficiencies were calculated as described previously (10,19).…”

Section: Methodsmentioning

confidence: 99%

“…Energy transfer between two different receptors may be due to true co-localization or may result from a high surface density of receptors, which would result in FET because of crowding on the platelet surface (19). To determine whether the observed FET was due to high receptor density (as opposed to true co-localization), we then examined the epitopes bound by mAbs AN51, SZ2, and IV.3 for homoassociation.…”

Section: Effects Of Mabs On Platelet Aggregation By Polymeric Igg-mentioning

confidence: 99%

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Physical Proximity and Functional Interplay of the Glycoprotein Ib-IX-V Complex and the Fc Receptor FcγRIIA on the Platelet Plasma Membrane

Sullam¹,

Hyun²,

Szöllősi³

et al. 1998

Journal of Biological Chemistry

142

116

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Although the glycoprotein (GP) Ib-IX-V complex andFc␥RIIA are distinct platelet membrane receptors, previous studies have suggested that these structures may be co-localized. To determine more directly the proximity of GP Ib-IX-V and Fc␥RIIA, we assessed the effects of anti-GP Ib␣ monoclonal antibodies on Fc␥RIIA-mediated platelet aggregation and on the direct binding of polymeric IgG to human platelets. In addition, we directly examined the proximity of Fc␥RII and GP Ib-IX-V using flow cytometric fluorescence energy transfer and immunoprecipitation studies. Preincubation of platelets with either of two monoclonal antibodies (AN51 or SZ2) directed against GP Ib␣ completely blocked platelet aggregation by polymeric IgG. Similarly, these antibodies totally inhibited platelet aggregation by two strains of viridans group streptococci known to induce aggregation via Fc␥RIIA. In addition, AN51 and SZ2 significantly reduced the binding of polymeric IgG to washed fixed platelets. When assessed by flow cytometry, significant levels of bidirectional energy transfer were detected between Fc␥RIIA and GP Ib␣, indicating a physical proximity of less than 10 nm between these receptors. This energy transfer was not due to high receptor density, because no homoassociative energy transfer was seen. Moreover, immunoprecipitation of Fc␥RIIA from platelet lysates also co-precipitated GP Ib␣. These results indicate that GP Ib␣ and Fc␥RIIA are co-localized on the platelet membrane and that this association is not random. The glycoprotein (GP)1 Ib-IX-V complex and Fc␥RIIA are distinct platelet membrane receptors for von Willebrand factor and polymeric IgG, respectively. The GP Ib-IX-V complex contains four polypeptides (GP Ib␣, GP Ib␤, GP IX, and GP V), which are present in a stoichiometry of 2:2:2:1 on the platelet plasma membrane (1). The precise configuration by which these peptides form a functional receptor is unknown, although more than one copy of each polypeptide per receptor complex is probable (1). This receptor mediates platelet adhesion to sites of blood vessel injury by binding von Willebrand factor in the subendothelium and participates in platelet activation by thrombin by providing a high affinity binding site for this agonist. In contrast to the GP Ib-IX-V complex, the platelet receptor for the Fc portion of IgG, Fc␥RIIA, is much simpler in structure, consisting of a single transmembrane polypeptide. This receptor is responsible for the aggregation and activation of platelets induced by immune complexes, opsonized bacteria, and certain antibodies that bind other platelet surface proteins (2).Although GP Ib-IX-V and Fc␥RIIA are structurally unrelated, a functional interaction between these receptors has been suspected for some time. Moore et al. reported that both polymeric IgG and IgG Fc fragments could inhibit platelet aggregation induced by von Willebrand factor and ristocetin (3). The reciprocal phenomenon was also observed, i.e. prior incubation of platelets with von Willebrand factor and ristocetin inhibited plate...

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Section: Methodsmentioning

confidence: 99%

Section: Effects Of Mabs On Platelet Aggregation By Polymeric Igg-mentioning

confidence: 99%

Physical Proximity and Functional Interplay of the Glycoprotein Ib-IX-V Complex and the Fc Receptor FcγRIIA on the Platelet Plasma Membrane

Sullam¹,

Hyun²,

Szöllősi³

et al. 1998

Journal of Biological Chemistry

142

116

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“…In contrast, no functional effects have been clearly shown for another lateral association of IR, i.e., that with the major histocompatibility complex (MHC) I molecules, mouse H2 and human HLA. Although the association of IR with these molecules has been demonstrated using biophysical and biochemical techniques (Fehlmann et al, 1985a;Phillips et al, 1986;Edidin and Reiland, 1990;Liegler et al, 1991), there is little evidence that this association has functional consequences for either IR or MHC I molecules. At best, some studies correlate MHC phenotype with insulin binding and signaling activity (Lafuse and Edidin, 1980;Kittur et al, 1987;Edidin, 1988), but others do not (Verland et al, 1989;Liegler et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Class I Human Leukocyte Antigen (HLA-I) Molecules with Insulin Receptors and Its Effect on the Insulin-Signaling Cascade

Ramalingam

Chakrabarti

Edidin

1997

MBoC

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Insulin receptor (IR) and class I major histocompatibility complex molecules associate with one another in cell membranes, but the functional consequences of this association are not defined. We found that IR and human class I molecules (HLA-I) associate in liposome membranes and that the affinity of IR for insulin and its tyrosine kinase activity increase as the HLA:IR ratio increases over the range 1:1 to 20:1. The same relationship between HLA:IR and IR function was found in a series of B-LCL cell lines. The association of HLA-I and IR depends upon the presence of free HLA heavy chains. All of the effects noted were reduced or abrogated if liposomes or cells were incubated with excess HLA-I light chain, ␤2-microglobulin. Increasing HLA:IR also enhanced phosphorylation of insulin receptor substrate-1 and the activation of phosphoinositide 3-kinase. HLA-I molecules themselves were phosphorylated on tyrosine and associated with phosphoinositide 3-kinase when B-LCL were stimulated with insulin. INTRODUCTIONThe manifold effects of insulin on cell physiology are mediated by a specific insulin receptor (IR). Insulin binding triggers a conformational change in IR, stimulating its tyrosine kinase activity and leading to its autophosphorylation (Rosen, 1987;White and Kahn, 1994). The insulin signal is propagated downstream of the IR kinase by the binding and tyrosine phosphorylation of docking proteins that connect IR to signaling pathways by mediating the binding of intracellular signaling proteins (Backer et al., 1992;Kuhne et al., 1993;Myers et al., 1994).IR has been shown to associate with other proteins in the plane of the plasma membrane. Some of these associations, i.e., with PC-1, a transmembrane glycoprotein (Maddux et al., 1995) and with ␤ adrenergic receptors (Karoor, et al., 1995;Baltensperger, et al., 1996), clearly have functional consequences. The first affects the kinase activity of IR, and the second affects the function of ␤ adrenergic receptors. In contrast, no functional effects have been clearly shown for another lateral association of IR, i.e., that with the major histocompatibility complex (MHC) I molecules, mouse H2 and human HLA. Although the association of IR with these molecules has been demonstrated using biophysical and biochemical techniques (Fehlmann et al., 1985a;Phillips et al., 1986;Edidin and Reiland, 1990;Liegler et al., 1991), there is little evidence that this association has functional consequences for either IR or MHC I molecules. At best, some studies correlate MHC phenotype with insulin binding and signaling activity (Lafuse and Edidin, 1980;Kittur et al., 1987;Edidin, 1988), but others do not (Verland et al., 1989;Liegler et al., 1991). Thus the consequences, if any, of the association between IR and MHC I molecules remain unclear.We have used a two-part strategy to detect the formation of molecular complexes between IR and human MHC I molecules, HLA, and to measure the functional consequences of this association for insulinmediated signaling and the state of MHC phosphorylati...

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“…Accordingly, dynamic receptor co-distribution patterns have been determined by a number of biophysical and biochemical techniques-e.g., f luorescence spectroscopy, electron and scanning force microscopies, chemical crosslinking, and co-isolation methods (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Such oligomeric assemblies have been described in different cellular systems at the surface of fixed and living cells in their native environments for a wide variety of receptors-e.g., among others the oligomeric structure of concanavalin A receptors or transferrin receptors; or the colocalization of interleukin 2 with HLA class I, class II, and intracellular adhesion molecule; that of the insulin receptor with major histocompatibility complex (MHC) molecules; or the supramolecular structure of the tetraspan molecules have been shown (4)(5)(6)(7)(8)(9)(10)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

HLA class I and II antigens are partially co-clustered in the plasma membrane of human lymphoblastoid cells

Jenei

Varga

Bene

et al. 1997

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

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Major histocompatibility complex (MHC) class II molecules displayed clustered patterns at the surfaces of T (HUT-102B2) and B (JY) lymphoma cells characterized by interreceptor distances in the micrometer range as detected by scanning force microscopy of immunogold-labeled antigens. Electron microscopy revealed that a fraction of the MHC class II molecules was also heteroclustered with MHC class I antigens at the same hierarchical level as described by the scanning force microscopy data, after specifically and sequentially labeling the antigens with 30-and 15-nm immunogold beads. On JY cells the estimated fraction of co-clustered HLA II was 0.61, whereas that of the HLA I was 0. Transmembrane receptors, antigens, and proteins have limited mobility in the plasma membrane, which can be described more precisely by a restricted diffusion model in contrast to the Singer-Nicolson fluid mosaic membrane model assuming complete diffusional freedom for membrane-bound molecules (1, 2). The limited mobility of receptor proteins may arise from extracellular, intramembrane, and intracytosolic connections. Membrane-bound molecules have a tendency to form oligomeric clusters. Accordingly, dynamic receptor co-distribution patterns have been determined by a number of biophysical and biochemical techniques-e.g., f luorescence spectroscopy, electron and scanning force microscopies, chemical crosslinking, and co-isolation methods (3-13). Such oligomeric assemblies have been described in different cellular systems at the surface of fixed and living cells in their native environments for a wide variety of receptors-e.g., among others the oligomeric structure of concanavalin A receptors or transferrin receptors; or the colocalization of interleukin 2 with HLA class I, class II, and intracellular adhesion molecule; that of the insulin receptor with major histocompatibility complex (MHC) molecules; or the supramolecular structure of the tetraspan molecules have been shown (4-10, 14-24).Apart from multisubunit receptor structures, where subunits must be together before or upon ligand binding, seemingly unrelated proteins are co-associated in many cases and held together in a dynamic cluster, apparently by weak interactions between proteins, or between proteins and lipid moieties in the plasma membrane. Considering the surface density of these membrane components, the probability of a diffusion driven random encounter for the formation and maintenance of oligomeric homo-and͞or heteroassociations without assuming cohesive forces is very low (13). Earlier theoretical and experimental considerations even suggested a genetic origin of the membrane lipid and protein mosaicism (9,25) The majority of the available experimental methods provides information only on the existence of receptor colocalization, without supplying further details on the degree of hetero-or homoclustering (13,15,26,27). Recently, the combined application of fluorescence spectroscopy with scanning force and electron microscopies has offered a unique method to study ...

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Proximity measurements between H-2 antigens and the insulin receptor by fluorescence energy transfer: evidence that a close association does not influence insulin binding.

Cited by 28 publications

References 42 publications

Physical Proximity and Functional Interplay of the Glycoprotein Ib-IX-V Complex and the Fc Receptor FcγRIIA on the Platelet Plasma Membrane

Physical Proximity and Functional Interplay of the Glycoprotein Ib-IX-V Complex and the Fc Receptor FcγRIIA on the Platelet Plasma Membrane

Interaction of Class I Human Leukocyte Antigen (HLA-I) Molecules with Insulin Receptors and Its Effect on the Insulin-Signaling Cascade

HLA class I and II antigens are partially co-clustered in the plasma membrane of human lymphoblastoid cells

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