Summary of the factors leading to Rac1 activation and downstream signaling, with enhanced transcription factor activity in endothelial cells, smooth muscle cells, and fibroblasts (discussed in text), along with a number of antagonizing factors
| Agonists Rac1 Activation | Kinases | Transcription Factors | |
|---|---|---|---|
| Vasoactive peptides: | Downstream of Rac1 activation: | Downstream of Rac1 activation: | |
| Angiotensin-II | PAK1 | NF-κB | |
| Endothelin-1 | JNK | AP-1 | |
| ANP | FAK | ATF2 | |
| MAPK | |||
| Proinflammatory protein: | Prevents Rac1 activation: | Prevents Rac1 activation: | |
| Endothelial cell | TNFα | ERK5 | KLF2 |
| Lipid (-like) molecules: | Nrf2 | ||
| Aldosterone | |||
| Sphingosine-1-phosphate | |||
| Bile acids | |||
| Growth factor: | |||
| VEGF | |||
| Vasoactive peptides: | Downstream of Rac1 activation: | Prevents Rac1 activation: | |
| Angiotensin-II | PAK1 | Nrf2 | |
| Endothelin-1 | JNK | ||
| Smooth muscle cell | Growth factors: | ERK1/2 | |
| PDGF | PKG | ||
| bFGF | MLCK (inhibition) | ||
| IGF-1 | |||
| Vasoactive peptide: | Downstream of Rac1 activation: | Downstream of Rac1 activation: | |
| Angiotensin-II | P38 | NF-κB | |
| Proinflammatory protein: | JAK | STAT3 | |
| TNFα | PI3K | Prevents Rac1 activation: | |
| Fibroblast | Growth factors: | JNK | STAT3 (negative feedback) |
| bFGF | Upstream of Rac1 activation: | ||
| TGFβ | ILK | ||
| NGF |
FAK, focal adhesion kinase; IGF-1, insulin-like growth factor-1; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; PKG, cGMP-dependent protein kinase.