Inhibitors of phosphoinositide 3-kinase block exocytosis but not endocytosis of transferrin receptors in 3T3-L1 adipocytes.
The role of PI 3-kinase in transferrin receptor recycling was investigated in 3T3-L1 adipocytes. Wortmannin, a specific PI 3-kinase inhibitor, blocked insulin stimulated recruitment of transferrin receptors to the plasma membrane (IC50 approximately 5-15 nM) with a similar potency to its inhibitory effects on PI 3-kinase and glucose transport. Wortmannin also blocked insulin stimulated recruitment of IGF-2 receptors to the cell surface. However, wortmannin (up to 200 nM) and another PI 3-kinase inhibitor, LY294002 (3 micrograms/ml), did not block transferrin receptor endocytosis. This demonstrates that while PI 3-kinase may be necessary for insulin stimulated exocytosis, it is not necessary for endocytosis of transferrin receptors.
Shepherd
P R
PR
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, UK.
Soos
M A
MA
Siddle
K
K
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D017527:Receptor, IGF Type 2 / Q000187:drug effects / Q000378:metabolism; D011990:Receptors, Transferrin / Q000187:drug effects / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007328:Insulin; D009025:Morpholines; D017527:Receptor, IGF Type 2; D011990:Receptors, Transferrin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D005947:Glucose; D000077191:Wortmannin