Molecular association between major histocompatibility complex class I antigens and insulin receptors in mouse liver membranes.

Fehlmann, Max; Peyron, Jean François; Samson, Michel; Obberghen, Emmanuel Van; Brandenburg, Dietrich; Brossette, Nicole

doi:10.1073/pnas.82.24.8634

Cited by 72 publications

(40 citation statements)

References 26 publications

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“…Our finding that cell HLA-I is phosphorylated on a tyrosine residue that is conserved in the cytoplasmic domains of HLA-A and HLA-B (but not HLA-C) was prefigured by experiments in vitro (Pober et al, 1978;Braydon et al, 1983;Guild and Strominger, 1984;Keith and Said, 1994). Later work showed that both human (HLA) and mouse (H-2) MHC-I molecules are phosphorylated on tyrosine when cells are stimulated by phorbol esters (Feurstein et al, 1985;Peyron and Fehlmann, 1988); some reports suggested that tyrosine phosphorylation of mouse H-2 molecules is stimulated by insulin (Fehlmann et al, 1985b;Peyron and Fehlmann, 1988;Burke et al, 1989).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…In most prior animal studies ofinsulin receptor function, the receptors were first partially purified, and then in vitro kinase assays were performed using exogenous phosphoacceptor substrates (21,35). Although informative, the latter approach is susceptible to biochemical artifacts resulting from cell homogenization and receptor purification procedures, e.g., proteolysis (36) and/or dephosphorylation of the receptor by contaminating phosphoprotein phosphatases (37), as well as removal ofthe receptor from the plasma membrane where interactions with other cellular components may influence receptor activity (38). Furthermore, differences in receptor kinase activity may be manifest in vitro with certain specific phosphoacceptor substrate proteins, but not with others (39).…”

Section: Discussionmentioning

confidence: 99%

Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resistance.

Saad¹,

Araki²,

Miralpeix³

et al. 1992

J. Clin. Invest.

297

189

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IntroductionInsulin rapidly stimulates tyrosine phosphorylation ofa protein of -185 kD in most cell types. This protein, termed insulin receptor substrate-I (IRS-1), has been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the present study we have examined the levels of IRS-1 and the phosphorylation state ofinsulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo in two rat models of insulin resistance, i.e., insulinopenic diabetes and fasting, and a mouse model of non-insulin-dependent diabetes mellitus (ob/ob) by immunoblotting with anti-peptide antibodies to IRS-1 and anti-phosphotyrosine antibodies. As previously described, there was an increase in insulin binding and a parallel increase in insulin-stimulated receptor phosphorylation in muscle of fasting and streptozotocin-induced (STZ) diabetic rats. There was also a modest increase in overall receptor phosphorylation in liver in these two models, but when normalized for the increase in binding, receptor phosphorylation was decreased, in liver and muscle of STZ diabetes and in liver of 72 h fasted rats. In the hyperinsulinemic ob/ob mouse there was a decrease in insulin binding and receptor phosphorylation in both liver and muscle. The tyrosyl phosphorylation of IRS-1 after insulin stimulation reflected an amplification of the receptor phosphorylation in liver and muscle of hypoinsulinemic animals (fasting and STZ diabetes) with a twofold increase, and showed a significant reduction ('-50%) in liver and muscle of ob/ob mouse. By contrast, the levels of IRS-1 protein showed a tissue specific regulation with a decreased level in muscle and an increased level in liver in hypoinsulinemic states of insulin resistance, and decreased levels in liver in the hyperinsulinemic ob/ob mouse. These data indicate that: (a) IRS-1 protein levels are differentially regulated in liver and muscle; (b) insulin levels may play a role in this differential regulation of IRS-1; (c) IRS-1 phosphorylation depends more on insulin receptor kinase activity than IRS-1 protein levels; and (d) Insulin resistance is characteristic of many disease states including non-insulin-dependent diabetes mellitus (NIDDM),' uncontrolled insulin-dependent diabetes, obesity, and prolonged fasting (1-4). Although various defects in insulin action have been reported in these conditions, the exact mechanisms involved in the insulin resistance have not been adequately defined. Insulin initiates its metabolic and growth-promoting effects by binding to the a subunit of its tetrameric receptor (5), thereby activating the kinase in the ,B subunit, which in turn catalyzes the intramolecular autophosphorylation of specific tyrosine residues of the 13 subunit, further enhancing the tyrosine kinase activity of the receptor toward other protein substrates (5-7). Considerable evidence demonstrates that insulin receptor tyrosine kinase activity is essential for many, if not all, of the biological effects of insulin ( 8-10).Although many ...

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“…Furthermore, it has been demonstrated that the products of phospholipase C hydrolysis, namely DG and PI3, may serve as intracellular second messengers. On the other hand, it was recently reported that major histocompatibility (HC) antigens (Ag), especially class I molecules, play an important role in some ligand-receptor interactions [4,5], including insulin [6][7][8][9], epidermal growth factor, luteinizing hormone [11] and 13-adrenergic receptors [11][12][13][14]. In the last case our group demonstrated that alloimmune anti-class I serum activation of cardiac fll-adrenoceptors leads to intracellular signaling by increasing cAMP production [14].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of phosphoinositide hydrolysis via class I antigen‐specific recognition in murine cardiac tissue

Cremaschi

Sterin‐Borda

1989

FEBS Letters

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Induction of polyphosphoinositide hydrolysis in cardiac tissue by specific recognition of class I histocompatibility antigens was assayed. C3H (H-2 k) mice auricles were labelled with myo-pH]inositol precursor and inositol phosphate production in the presence or absence of anti-class I k products was measured. Anti-class I, but not anti-class II products specifically increased phosphoinositide turnover. This increment was partially blocked by muscarinic cholinergic and ct-adrenergic blockers and even more so by the phospholipase C inhibitor NCDC. Alloantibodies specifically directed against class I antigens could then exert stimulation of phospholipase C-mediated phosphoinositide hydrolysis through the interaction with muscarinic cholinergic and/or ~-adrenergic receptors. The induction of intraceUular second messengers by class I antigens and hormone-receptor interactions is discussed.

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Molecular association between major histocompatibility complex class I antigens and insulin receptors in mouse liver membranes.

Cited by 72 publications

References 26 publications

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

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

Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resistance.

Stimulation of phosphoinositide hydrolysis via class I antigen‐specific recognition in murine cardiac tissue

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