J Biol Chem. 2012 May 11;287(20):16917-29. doi: 10.1074/jbc.M111.329979. Epub 2012 Mar 28.

Transforming growth factor-beta1 regulates Cdk5 activity in primary sensory neurons.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Utreras, E., Keller, J., Terse, A., Prochazkova, M., Iadarola, M. J., Kulkarni, A. B.,
["Functional Genomics Section, Laboratory of Cell and Developmental Biology, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA."]
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.
PMID: 22451679External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 CDK5 In vitro PTM assay Phosphorylation 22451679
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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