Canonical and non-canonical Notch signaling in CD4⁺ T cells

Curr Top Microbiol Immunol. 2012;360:99-114. doi: 10.1007/82_2012_233.


For T cells to become fully activated, they must integrate a myriad of signals, both extrinsic and intrinsic. External stimuli accrued through various cell surface receptors are transduced and amplified through a coordinated circuitry of signaling cascades that ultimately result in the transcription of new genes. Along the way, extracellular and intracellular signaling components function to impart a fully activated state. Evidence is accumulating to show that the Notch family of cell surface receptors, long known to function as transcriptional regulators through their interactions with the canonical nuclear binding protein CSL/RBP-J, may also be playing an as-yet-unappreciated role in T cell activation by virtue of its signaling via non-canonical as well as nonnuclear mechanisms. In this review we will discuss these and other better-known means by which Notch signaling influences T cell responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
  • Lymphocyte Activation / genetics
  • Mice
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • MAML1 protein, human
  • RBPJ protein, human
  • Receptors, Notch
  • Transcription Factors
  • Amyloid Precursor Protein Secretases