title: Evidence that truncated TrkB isoform, TrkB-Shc can regulate phosphorylated TrkB protein levels.
abstract: Tropomyosin receptor kinase B (TrkB) is best known as the receptor for brain-derived neurotrophic factor (BDNF). In humans, three major isoforms of TrkB, the full-length receptor (TrkB-TK+) and two C-terminal truncated receptors (TrkB-TK- and TrkB-Shc) are expressed in various tissues. In comparison to TrkB-TK+ and TrkB-TK-, TrkB-Shc is less well characterized. In this study, we analyzed the biological function of the TrkB-Shc receptor in response to exogenous BDNF treatment. In experiments transiently overexpressing TrkB-Shc in CHOK1 cells, we found that TrkB-Shc protein levels were rapidly decreased when cells were exposed to exogenous BDNF. When we assessed the functional impact of TrkB-Shc on TrkB-TK+ activity, we found that phosphorylated TrkB-TK+ protein levels were significantly decreased in the presence of TrkB-Shc and moreso following BDNF exposure. Interestingly, while the reduction of phosphorylated TrkB-TK+ protein was more pronounced in the presence of TrkB-Shc following BDNF exposure, the stability of TrkB-Shc protein itself was increased. Our findings suggest that cells may increase TrkB-Shc protein levels in response to exogenous BDNF exposure to regulate TrkB-TK+ activity by increasing degradation of activated receptor complexes as a means to prevent overactivation or inappropriate temporal and spatial activation of BDNF/TrkB-TK+ signaling.
authors.affiliation: Illawarra Health and Medical Research Institute and the School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia. jwong@uow.edu.au
authors.forename: Jenny
authors.initials: J
authors.lastname: Wong
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010766:Phosphorylation; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007527:Isoenzymes; D020813:Receptor, trkB