Reference

12/15-Lipoxygenase (12/15-LOX) plays a significant role in the activation of signal transducer and activator of transcription 3 (STAT3) induced by platelet-derived growth factor (PDGF). Here's how it contributes to this process:

1. Signaling Hub: 12/15-LOX is identified as an important signaling hub in PDGF-triggered STAT3 activation. This enzyme's activity is crucial for the activation of Src kinase, which is upstream of STAT3 activation. When PDGF is introduced, it stimulates 12/15-LOX, leading to subsequent activation events that include Src and STAT3 source.

2. Inhibition of Activation: Studies have shown that small molecules like indirubin-3′-monoxime (I3MO) can inhibit the activation of STAT3 by impairing the activity of 12/15-LOX. This inhibition results in blunting the PDGF-induced reactive oxygen species (ROS) and lipid peroxides production, which are necessary for the promotion of STAT3 signaling source.

3. Lipid Peroxide Production: The lipid peroxides derived from 12/15-LOX, such as 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), are involved in signaling events that contribute to the modification of proteins necessary for STAT3 activation. These lipid peroxides can affect the oxidation state of protein tyrosine phosphatases, influencing downstream signaling pathways source.

In summary, 12/15-Lipoxygenase facilitates PDGF-induced STAT3 activation by acting as a critical mediator in the signaling pathway, influencing both kinase activity and oxidative signaling events.