NGF (nerve growth factor) binding to TrkA (tropomyosin receptor kinase A) induces dimerization, autophosphorylation and internalization of the receptor to signalling vesicles for delivery of differentiation signals. TrkA interacts with p75 receptor through the p62–TRAF-6 (tumour-necrosis-factor-receptor-associated factor 6) complex bridging the two receptors. The atypical protein kinase C is activated and recruited to the receptor complex as well. TrkA is Lys63-polyubiquitinated on Lys485 by the E3 (ubiquitin ligase), TRAF-6, and E2 (ubiquitin-conjugating enzyme), UbcH7. Inhibition of polyubiquitination has been observed to interrupt signalling and internalization. Furthermore, an absence of p62 prevents endosomal localization and signalling. Altogether, these findings reveal Lys63-linked polyubiquitin chains and the shuttling protein p62 co-ordinately regulate TrkA internalization, trafficking and sorting.
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Conference Article| October 25 2006
The role of ubiquitin in neurotrophin receptor signalling and sorting
M.W. Wooten 1
1Program in Cellular and Molecular Biosciences, Department of Biological Sciences, 331 Funchess Hall, Auburn University, Auburn, AL 36849, U.S.A.
1To whom correspondence should be addressed (email firstname.lastname@example.org).
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M.W. Wooten, T. Geetha; The role of ubiquitin in neurotrophin receptor signalling and sorting. Biochem Soc Trans 1 October 2006; 34 (5): 757–760. doi: https://doi.org/10.1042/BST0340757
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