TY - JOUR T1 - TrkA <em>In Vivo</em> Function Is Negatively Regulated by Ubiquitination JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4090 LP - 4098 DO - 10.1523/JNEUROSCI.4294-13.2014 VL - 34 IS - 11 AU - Erkan Kiris AU - Ting Wang AU - Sudhirkumar Yanpallewar AU - Susan G. Dorsey AU - Jodi Becker AU - Sina Bavari AU - Mary Ellen Palko AU - Vincenzo Coppola AU - Lino Tessarollo Y1 - 2014/03/12 UR - http://www.jneurosci.org/content/34/11/4090.abstract N2 - TrkA is a tyrosine kinase receptor required for development and survival of the peripheral nervous system. In the adult, TrkA and its ligand NGF are peripheral pain mediators, particularly in inflammatory pain states. However, how TrkA regulates the function of nociceptive neurons and whether its activity levels may lead to sensory abnormalities is still unclear. Here we report the characterization of a 3 aa (KFG) domain that negatively regulates TrkA level and function in response to NGF. Deletion of this domain in mouse causes a reduction of TrkA ubiquitination leading to an increase in TrkA protein levels and activity. The number of dorsal root ganglia neurons is not affected by the mutation. However, mutant mice have enhanced thermal sensitivity and inflammatory pain. Together, these data suggest that ubiquitination is a mechanism used in nociceptive neurons to regulate TrkA level and function. Our results may enhance our understanding of how ubiquitination affects TrkA activation following noxious thermal stimulation and inflammatory pain. ER -