Inhibition of Rab5 Activation During Insulin Receptor-Mediated Endocytosis
Current Cellular Biochemistry
Endosome Fusion, Receptor Tyrosine Kinase, Small GTPases, Kinase Inhibitors
Activation of receptor tyrosine kinases is a key feature in receptor signaling and membrane trafficking processes. In this study, we found that
the insulin receptor tyrosine kinase activity is required for fusion between early endosomes. AG1024, a receptor tyrosine kinase inhibitor,
blocked the in vitro endosome fusion in a concentration-dependent manner. We observed that Rab5: wild type partially rescued the fusion
reaction, whereas Rab5: Q79L mutant fully rescued it. We also observed that treatment of cells with insulin receptor kinase inhibitor
HNMPA-(AM)3 blocked the formation of Rab5-positive endosomes as well as the activation of Rab5 upon addition of insulin in intact cells.
HNMPA-(AM)3 inhibitor also affected the endosomal co-localization of Rab5 and insulin receptor. However, the formation of Rab5: Q79L
mutant-positive endosomes were not affected by the HNMPA-(AM)3 inhibitor. In addition, HNMPA-(AM)3 inhibitor affected the association
of Rin1 to membrane upon insulin stimulation. Furthermore, Rin1 did not fully support endosome fusion in the presence of the AG1024
inhibitor. These results constitute the first evidence that, at least in part, the enzymatic activity of insulin receptor is required for the fusion
events via the activation of Rab5.
Jozic, Ivan; Gustavo Blanco; and M. Alejandro Barbieri. 2011. "Inhibition of Rab5 Activation During Insulin Receptor-Mediated Endocytosis." Current Cellular Biochemistry 1, (1): 20-32. http://nsuworks.nova.edu/cnso_bio_facarticles/16