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Brefeldin A inhibits insulin‐dependent receptor redistribution in HIRcB cells
Author(s) -
Shome Kuntala,
Xu Xiao-qin,
Romero Guillermo
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01310-w
Subject(s) - brefeldin a , insulin , insulin receptor , insulin receptor substrate , receptor , endocrinology , medicine , tyrosine kinase , irs2 , receptor tyrosine kinase , stimulation , biology , chemistry , microbiology and biotechnology , insulin resistance , golgi apparatus , endoplasmic reticulum
Brefeldin A (BFA) is a potent inhibitor of intracellular vesicle traffic. We have investigated the effects of BFA on the traffic of the insulin receptor in HIRcB cells, a cell line derived from Rat‐1 fibroblasts that over‐expresses a normal human insulin receptor. We report here that insulin‐dependent receptor redistribution is inhibited by BFA and that this drug has no effects on the insulin‐independent redistribution of the receptor. Autophosphorylation of the insulin receptor and the stimulation of mitogen‐activated protein kinase (MAPK) by insulin were not affected by treatment with the drug. The effects of BFA were further shown to require addition of the drug prior to the addition of insulin. BFA added 10 min after stimulation with insulin had no effects on the redistribution of the receptor. Dose‐response studies demonstrated that the effects of BFA were half‐maximal at a dose of 1 μg/ml and maximal at about 10 μg/ml. These findings suggest that BFA blocks an early step in the chain of events that lead to insulin receptor internalization without affecting the interactions of the receptor with insulin, the stimulation of the tyrosine kinase activity of the receptor by the hormone, or other insulin‐regulated signalling pathways, such as the activation of MAPK.