S100B's double life: intracellular regulator and extracellular signal

Biochim Biophys Acta. 2009 Jun;1793(6):1008-22. doi: 10.1016/j.bbamcr.2008.11.009. Epub 2008 Dec 7.


The Ca2+-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular functions. Recent studies have provided more detailed information concerning the mechanism(s) of action of S100B as an intracellular regulator and an extracellular signal. Indeed, intracellular S100B acts as a stimulator of cell proliferation and migration and an inhibitor of apoptosis and differentiation, which might have important implications during brain, cartilage and skeletal muscle development and repair, activation of astrocytes in the course of brain damage and neurodegenerative processes, and of cardiomyocyte remodeling after infarction, as well as in melanomagenesis and gliomagenesis. As an extracellular factor, S100B engages RAGE (receptor for advanced glycation end products) in a variety of cell types with different outcomes (i.e. beneficial or detrimental, pro-proliferative or pro-differentiative) depending on the concentration attained by the protein, the cell type and the microenvironment. Yet, RAGE might not be the sole S100B receptor, and S100B's ability to engage RAGE might be regulated by its interaction with other extracellular factors. Future studies using S100B transgenic and S100B null mice might shed more light on the functional role(s) of the protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Communication / physiology*
  • Cell Differentiation
  • Cell Proliferation
  • Cytoskeleton / metabolism
  • Humans
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / genetics
  • S100 Proteins / metabolism*
  • Signal Transduction / physiology*


  • Nerve Growth Factors
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • S100B protein, human
  • S100b protein, mouse
  • Calcium