Proteomic Analysis Reveals a Role for RSK in p120-catenin Phosphorylation and Melanoma Cell-Cell Adhesion

Mol Cell Proteomics. 2020 Jan;19(1):50-64. doi: 10.1074/mcp.RA119.001811. Epub 2019 Nov 2.

Abstract

The RAS/mitogen-activated protein kinase (MAPK) signaling pathway regulates various biological functions, including cell survival, proliferation and migration. This pathway is frequently deregulated in cancer, including melanoma, which is the most aggressive form of skin cancer. RSK (p90 ribosomal S6 kinase) is a MAPK-activated protein kinase required for melanoma growth and proliferation, but relatively little is known about its function and the nature of its cellular partners. In this study, we used a proximity-based labeling approach to identify RSK proximity partners in cells. We identified many potential RSK-interacting proteins, including p120ctn (p120-catenin), which is an essential component of adherens junction (AJ). We found that RSK phosphorylates p120ctn on Ser320, which appears to be constitutively phosphorylated in melanoma cells. We also found that RSK inhibition increases melanoma cell-cell adhesion, suggesting that constitutive RAS/MAPK signaling negatively regulates AJ integrity. Together, our results indicate that RSK plays an important role in the regulation of melanoma cell-cell adhesion.

Keywords: BRAF; Cell-cell interactions; MAPK; RSK; adherens junction; melanoma; p120ctn; phosphorylation; protein kinases; protein-protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catenins / genetics
  • Catenins / metabolism*
  • Cell Adhesion / genetics*
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • MAP Kinase Signaling System / genetics
  • Melanoma / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Proteomics / methods*
  • RNA Interference
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Signal Transduction / genetics

Substances

  • Catenins
  • delta catenin
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3
  • Mitogen-Activated Protein Kinases

Grant support