Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases

Trends Cell Biol. 2001 Jun;11(6):258-66. doi: 10.1016/s0962-8924(01)01990-0.


Signaling through receptor tyrosine kinases (RTKs) is a major mechanism for intercellular communication during development and in the adult organism, as well as in disease-associated processes. The phosphorylation status and signaling activity of RTKs is determined not only by the kinase activity of the RTK but also by the activities of protein tyrosine phosphatases (PTPs). This review discusses recently identified PTPs that negatively regulate various RTKs and the role of PTP inhibition in ligand-induced RTK activation. The contributions of PTPs to ligand-independent RTK activation and to RTK inactivation by other classes of receptors are also surveyed. Continued investigation into the involvement of PTPs in RTK regulation is likely to unravel previously unrecognized layers of RTK control and to suggest novel strategies for interference with disease-associated RTK signaling.

Publication types

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

MeSH terms

  • Cell Communication / physiology
  • Dimerization
  • Humans
  • Models, Animal
  • Phosphorylation
  • Protein Tyrosine Phosphatases / physiology*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / physiology*
  • Substrate Specificity


  • Receptor Protein-Tyrosine Kinases
  • Protein Tyrosine Phosphatases