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Abstract
Shoc2 is a positive regulator of signaling to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Shoc2 is also proposed to interact with RAS and Raf-1 in order to accelerate ERK1/2 activity. To understand the mechanisms by which Shoc2 regulates ERK1/2 activation by the epidermal growth factor receptor (EGFR), we dissected the role of Shoc2 structural domains in binding to its signaling partners and its role in regulating ERK1/2 activity. Shoc2 is comprised of two main domains: the 21 leucine rich repeats (LRRs) core and the N-terminal non-LRR domain. We demonstrated that the N-terminal domain mediates Shoc2 binding to both M-Ras and Raf-1, while the C-terminal part of Shoc2 contains a late endosomal targeting motif. We found that M-Ras binding to Shoc2 is independent of its GTPase activity. While overexpression of Shoc2 did not change kinetics of ERK1/2 activity, both the N-terminal and the LRR-core domain were able to rescue ERK1/2 activity in cells depleted of Shoc2, suggesting that these Shoc2 domains are involved in modulating ERK1/2 activity.
Document Type
Article
Publication Date
6-21-2013
Digital Object Identifier (DOI)
http://dx.doi.org/10.1371/journal.pone.0066067
Repository Citation
Jeoung, Myoungkun; Abdelmoti, Lina; Jang, Eun Ryoung; Vander Kooi, Craig W.; and Galperin, Emilia, "Functional Integration of the Conserved Domains of Shoc2 Scaffold" (2013). Molecular and Cellular Biochemistry Faculty Publications. 7.
https://uknowledge.uky.edu/biochem_facpub/7
Supporting documents
Notes/Citation Information
Published in PLoS ONE, v. 8, no. 6, e66067.
© 2013 Jeoung et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.