Shoc2/Sur8 protein regulates neurite outgrowth

PLoS One. 2014 Dec 16;9(12):e114837. doi: 10.1371/journal.pone.0114837. eCollection 2014.

Abstract

The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Enzyme Activation / genetics
  • Epidermal Growth Factor / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MAP Kinase Signaling System
  • Neurites / metabolism*
  • PC12 Cells
  • Phosphorylation
  • RNA Interference
  • RNA, Small Interfering
  • Rats
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • SHOC2 protein, human
  • Shoc2 protein, rat
  • Epidermal Growth Factor
  • Extracellular Signal-Regulated MAP Kinases
  • ras Proteins

Grants and funding

GL, TG and LMD were recipients of fellowships from the Ministerio de Educación y Ciencia (MEC) (to GL, TG), and Fondo de Investigaciones Sanitarias (FIS) (to LMD). LSR held a postdoctoral research contract from CIBERNED. This work was supported by FIS grant (PI10/00815) to JLO; CIBERNED to MC; SAF2008-01951, Comunidad Autónoma de Madrid (CAM) S-SAL-0202-2006-01 and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) to TI; FIS grant PI12/00775 and ISCIII-RETIC (Red Temática de Investigación Cooperativa en Cáncer) RD12/0036/0027 from the Instituto de Salud Carlos III to PSG; and FIS grants (PI09/0562 and PI13/00703), ISCIII-RETIC (RD06/0020/0003 and RD12/0036/0021), and the Spanish Association Against Cancer (AECC) to JMR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.