Table 1.
Classification of RTK signaling modulators according to their spatiotemporal feedback
| Feedback | Modulator | Target/Pathway | Signaling Output |
Mechanism of Action |
|---|---|---|---|---|
| Late, reversible | Anosmin 1 | FGFR | Amplification | FGF-FGFR signaling complex assembly and stabilization |
| DUSP6 | FGF-MAPK | Attenuation | Dephosphorylation of ERK | |
| FLRT family | FGFR | Amplification | FGF-FGFR signaling complex activation | |
| MIG6 | ErbB receptor family | Attenuation | Inhibition of ErbB receptor family dimerization | |
| SEF | FGF-MAPK/ERK & FGF-PI3K/AKT | Attenuation | FGF-FGFR signaling complex assembly and activation | |
| SPRED | FGF-RAS/RAF | Attenuation | Inhibition of RAF activation | |
| Sprouty family | RAS/MAPK & RAS/PI3K | Attenuation | Inhibition of downstream effector signaling | |
| Early, reversible | PTEN | PI3K/AKT | Attenuation | Dephosphorylation of PIP3 |
| RKIP | RAF/MEK | Attenuation | Inhibition of RAF1 and MEK interaction | |
| SHP2 | EGFR, FGF-MAPK/ERK, IR, & RET | Amplification | Dephosphorylation of inhibitory modulators of downstream effectors | |
| Late, irreversible | CNPY1 | FGFR | Amplification | FGFR maturation |
| LRIG family | ErbB receptor family, MET, & RET | Attenuation | Receptor ubiquitination and degradation | |
| SOCS family | c-KIT, EGFR, FLT3, IGF-1R, & IR | Attenuation | Receptor ubiquitination and degradation | |
| Early, irreversible | CBL family | EGFR, MET, PDGFR, & RET | Attenuation | Receptor ubiquitination and degradation |
| NEDD4 & NEDD4L | ErbB receptor family, FGFR, IGF-1R, IR, NRTK1, & VEGFR | Attenuation | Receptor ubiquitination and degradation | |
| NRDP1 | ERBB3 | Attenuation | ERBB3 trafficking and ubiquitination | |
| SHISA2 | FGFR | Attenuation | Receptor maturation and ubiquitination |