CNK2 couples NGF signal propagation to multiple regulatory cascades driving cell differentiation

Curr Biol. 2004 Mar 9;14(5):439-45. doi: 10.1016/j.cub.2004.02.037.


Neuronal precursor cells have the capacity to engage the Raf-MEK-ERK signal module to drive either of two distinctly different regulatory programs, proliferation and differentiation. This is, at least in part, a consequence of stimulus-specific shaping of the kinase cascade response. For example, the mitogen EGF induces a transient ERK activation, whereas the neurotrophin NGF induces prolonged ERK activation. Here we define a novel component of the regulatory machinery contributing to the selective integration of MAP kinase signaling with discrete biological responses. We show that the scaffold/adaptor protein CNK2/MAGUIN-1 is required for NGF- but not EGF-induced ERK activation. In addition, CNK2 makes a separate, essential contribution to the coupling of NGF signaling to membrane/cytoskeletal remodeling. We propose that CNK2 integrates multiple regulatory pathways that must function in concert to drive an appropriate biological response to external stimuli.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Cell Differentiation / physiology*
  • DNA Primers
  • Enzyme Activation
  • Gene Expression / physiology*
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • MAP Kinase Signaling System / physiology
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Microfilament Proteins
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / physiology
  • Nerve Growth Factor / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Neurites / metabolism
  • PC12 Cells
  • Plasmids / genetics
  • Precipitin Tests
  • RNA, Small Interfering / genetics
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / metabolism


  • Adaptor Proteins, Signal Transducing
  • CNKSR2 protein, human
  • Carrier Proteins
  • Cnksr2 protein, rat
  • DNA Primers
  • EPB41L3 protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • Nerve Growth Factor
  • Mitogen-Activated Protein Kinases