Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases

Nature. 2000 Apr 27;404(6781):999-1003. doi: 10.1038/35010121.


The Src family of protein tyrosine kinases (Src-PTKs) is important in the regulation of growth and differentiation of eukaryotic cells. The activity of Src-PTKs in cells of different types is negatively controlled by Csk, which specifically phosphorylates a conserved regulatory tyrosine residue at the carboxy-terminal tail of the Src-PTKs. Csk is mainly cytoplasmic and Src-PTKs are predominantly membrane-associated. This raises a question about the mechanism of interaction between these enzymes. Here we present Cbp--a transmembrane phosphoprotein that is ubiquitously expressed and binds specifically to the SH2 domain of Csk. Cbp is involved in the membrane localization of Csk and in the Csk-mediated inhibition of c-Src. In the plasma membrane Cbp is exclusively localized in the GM1 ganglioside-enriched detergent-insoluble membrane domain, which is important in receptor-mediated signalling. These findings reveal Cbp as a new component of the regulatory mechanism controlling the activity of membrane-associated Src-PTKs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / enzymology
  • Brain / metabolism
  • COS Cells
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • DNA, Complementary
  • Enzyme Activation
  • Enzyme Activators
  • Escherichia coli
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Phosphoproteins / genetics
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tissue Distribution
  • src Homology Domains
  • src-Family Kinases / metabolism*


  • DNA, Complementary
  • Enzyme Activators
  • Membrane Proteins
  • Pag1 protein, rat
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • src-Family Kinases

Associated data

  • GENBANK/AB038038