Interaction of class I human leukocyte antigen (HLA-I) molecules with insulin receptors and its effect on the insulin-signaling cascade.
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.
Ramalingam
T S
TS
Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Chakrabarti
A
A
Edidin
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D004735:Energy Transfer; D004789:Enzyme Activation / Q000187:drug effects; D005453:Fluorescence; D005456:Fluorescent Dyes; D006021:Glycophorins / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007700:Kinetics; D008081:Liposomes / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013816:Thermodynamics; D001613:beta 2-Microglobulin / Q000378:metabolism / Q000494:pharmacology
D000255:Adenosine Triphosphate; D005456:Fluorescent Dyes; D006021:Glycophorins; D015789:HLA-A2 Antigen; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008081:Liposomes; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D019000:Phosphotyrosine; D011972:Receptor, Insulin; D001613:beta 2-Microglobulin; C526292:IRS1 protein, human