Homologous down-regulation of the insulin receptor is associated with increased receptor biosynthesis in cultured human lymphocytes (IM-9 line).

AUTOR(ES)

Rouiller, D G

RESUMO

Cultured IM-9 lymphocytes were preincubated with 1 microM insulin, a condition resulting in a 56% reduction in cell surface insulin receptors. Cellular proteins were then metabolically labeled, and the radioactivity incorporated into the insulin proreceptor and receptor mature subunits was measured over a 4-hr chase period. As early as 30 min of chase, incorporation into the proreceptor was 28 +/- 6% higher in down-regulated cells than in control cells (mean +/- SEM, P less than 0.05). By 1 hr of chase, the difference reached 41 +/- 14% for the proreceptor and 84 +/- 28% for the alpha subunit (P less than 0.01); values returned to normal by 2 hr. At 4 hr of chase, labeling of the alpha subunit of down-regulated cells was diminished 36 +/- 9% below control (P less than 0.05). The increased biosynthetic rate of the proreceptor was more prominent when the chase medium contained 25 microM monensin, an inhibitor of processing of the proreceptor into mature subunits. Similar effects occurred whether [3H]mannose or [3H]lysine was used as biosynthetic marker. The effect was specific for the insulin receptor. These data demonstrate that insulin receptor homologous down-regulation is associated with increased proreceptor biosynthesis and processing into mature subunits. This might represent a cellular mechanism compensating for insulin-induced receptor loss.

Documentos Relacionados

• Induction of the insulin proreceptor by hydrocortisone in cultured lymphocytes (IM-9 line).
• Glucocorticoid regulation of insulin receptor gene transcription in IM-9 cultured lymphocytes.
• Is telomerase reactivation associated with the down-regulation of TGF β receptor-II expression in human breast cancer?
• Intracellular potassium depletion in IM-9 lymphocytes suppresses the slowly dissociating component of human growth hormone binding and the down-regulation of its receptors but does not affect insulin receptors.
• Biosynthetic labeling of insulin receptor: studies of subunits in cultured human IM-9 lymphocytes.