| First Author | Utreras E | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 20 | Pages | 16917-29 |
| PubMed ID | 22451679 | Mgi Jnum | J:185442 |
| Mgi Id | MGI:5428793 | Doi | 10.1074/jbc.M111.329979 |
| Citation | Utreras E, et al. (2012) Transforming growth factor-beta1 regulates Cdk5 activity in primary sensory neurons. J Biol Chem 287(20):16917-29 |
| abstractText | In addition to many important roles for Cdk5 in brain development and synaptic function, we reported previously that Cdk5 regulates inflammatory pain signaling, partly through phosphorylation of transient receptor potential vanilloid 1 (TRPV1), an important Na(+)/Ca(2+) channel expressed in primary nociceptive afferent nerves. Because TGF-beta regulates inflammatory processes and its receptor is expressed in TRPV1-positive afferents, we studied the cross-talk between these two pathways in sensory neurons during experimental peripheral inflammation. We demonstrate that TGF-beta1 increases transcription and protein levels of the Cdk5 co-activator p35 through ERK1/2, resulting in an increase in Cdk5 activity in rat B104 neuroblastoma cells. Additionally, TGF-beta1 enhances the capsaicin-induced Ca(2+) influx in cultured primary neurons from dorsal root ganglia (DRG). Importantly, Cdk5 activity was reduced in the trigeminal ganglia and DRG of 14-day-old TGF-beta1 knock-out mice, resulting in reduced Cdk5-dependent phosphorylation of TRPV1. The decreased Cdk5 activity is associated with attenuated thermal hyperalgesia in TGF-beta1 receptor conditional knock-out mice, where TGF-beta signaling is significantly reduced in trigeminal ganglia and DRG. Collectively, our results indicate that active cross-talk between the TGF-beta and Cdk5 pathways contributes to inflammatory pain signaling. |
