A monomer-dimer model explains the results of radiation inactivation: binding characteristics of insulin receptor purified from human placenta.
The technique of radiation inactivation has been used on highly purified human placental insulin receptor in order to determine the functional molecular size responsible for the insulin binding and to evaluate the "affinity regulator" hypothesis, which has been proposed to explain the increase in specific insulin binding to rat liver membranes observed at low radiation doses [Harmon, J. T., Hedo, J. A., & Kahn, C. R. (1983) J. Biol. Chem. 258, 6875-6881]. Three different types of inactivation curves were observed: (1) biphasic with an enhanced binding activity after exposure to low radiation doses, (2) nonlinear with no change in binding activity after exposure to low radiation doses, and (3) linear with a loss in the binding activity with increasing radiation exposures. A monomer-dimer model was the simplest model that best described the three types of radiation inactivation curves observed. The model predicts that an increase in insulin binding activity would result after exposure to low radiation doses when the initial dimer/monomer ratio is equal to or greater than 1 and a monomer is more active than a dimer. The monomer size of the binding activity was estimated to be 227,000 daltons by this model. This value most likely reflects the size of the monomeric alpha beta form. To substantiate this model, the purified receptor was fractionated by Sepharose CL-6B chromatography. The insulin binding profile of this column indicated two peaks.(ABSTRACT TRUNCATED AT 250 WORDS)
Fujita-Yamaguchi
Y
Y
Department of Molecular Genetics, Beckman Research Institute of the City of Hope, Duarte, California 91010.
Harmon
J T
JT
D002462:Cell Membrane / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008962:Models, Theoretical; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism / Q000528:radiation effects*
D007328:Insulin; D046911:Macromolecular Substances; D011972:Receptor, Insulin