Figure 6. Proposed Model of Microtubule Role in VEGFR2 Signaling.

This model is based on the findings presented in this study. VEGFR2 exists in an equilibrium concentration on endothelial cell membranes due to its constant internalization and recycling. (A) The disruption of microtubules causes this equilibrium membrane concentration to increase indicating that it is either interfering with uptake or recycling of the receptor to the membrane. In response to VEGF, VEGFR2 becomes phosphorylated, internalizes and activates second messenger molecules such as ERK1/2. (B) We propose that VEGFR2 is trafficked along microtubules after VEGF activation thus increasing the likelihood that it will come in contact with MAP Kinases such as ERK1/2 that are known to associate with the microtubule cytoskeleton. In the absence of microtubules, the immediate phosphorylation of ERK1/2 is much less efficient. Finally, the total VEGFR2 amounts in the cell are dictated by the rate of degradation of the receptor. (C) Since actin and microtubule disruption changes total levels of VEGFR2, it is likely that the cytoskeleton also plays a function in increasing the efficiency of receptor degradation in response to VEGF.