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PLoS One. 2013 Jun 21;8(6):e66067. doi: 10.1371/journal.pone.0066067. Print 2013.

Functional Integration of the Conserved Domains of Shoc2 Scaffold.

Author information

1
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.

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.

PMID:
23805200
PMCID:
PMC3689688
DOI:
10.1371/journal.pone.0066067
[Indexed for MEDLINE]
Free PMC Article

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