PMID- 9398668 OWN - NLM STAT- MEDLINE DCOM- 20000728 LR - 20240322 IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 8 IP - 12 DP - 1997 Dec TI - Interaction of class I human leukocyte antigen (HLA-I) molecules with insulin receptors and its effect on the insulin-signaling cascade. PG - 2463-74 AB - 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, beta2-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. FAU - Ramalingam, T S AU - Ramalingam TS AD - Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA. FAU - Chakrabarti, A AU - Chakrabarti A FAU - Edidin, M AU - Edidin M LA - eng GR - R01 AI014584/AI/NIAID NIH HHS/United States GR - R37-AI14584/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (Fluorescent Dyes) RN - 0 (Glycophorins) RN - 0 (HLA-A2 Antigen) RN - 0 (IRS1 protein, human) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Liposomes) RN - 0 (Phosphoproteins) RN - 0 (beta 2-Microglobulin) RN - 21820-51-9 (Phosphotyrosine) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 2.7.10.1 (Receptor, Insulin) SB - IM MH - Adenosine Triphosphate/metabolism MH - B-Lymphocytes/cytology/drug effects/enzymology/metabolism MH - Cell Line MH - Energy Transfer MH - Enzyme Activation/drug effects MH - Fluorescence MH - Fluorescent Dyes MH - Glycophorins/metabolism MH - HLA-A2 Antigen/chemistry/*metabolism/*pharmacology MH - Humans MH - Insulin/metabolism/*pharmacology MH - Insulin Receptor Substrate Proteins MH - Kinetics MH - Liposomes/drug effects/metabolism MH - Phenotype MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoproteins/metabolism MH - Phosphorylation/drug effects MH - Phosphotyrosine/metabolism MH - Protein Binding MH - Receptor, Insulin/*metabolism MH - Signal Transduction/*drug effects MH - Thermodynamics MH - beta 2-Microglobulin/metabolism/pharmacology PMC - PMC25720 EDAT- 1997/12/17 02:42 MHDA- 2000/08/06 11:00 CRDT- 1997/12/17 02:42 PHST- 1997/12/17 02:42 [pubmed] PHST- 2000/08/06 11:00 [medline] PHST- 1997/12/17 02:42 [entrez] AID - 10.1091/mbc.8.12.2463 [doi] PST - ppublish SO - Mol Biol Cell. 1997 Dec;8(12):2463-74. doi: 10.1091/mbc.8.12.2463.