Protein tyrosine phosphatases as negative regulators of mitogenic signaling

J Cell Physiol. 1999 Aug;180(2):173-81. doi: 10.1002/(SICI)1097-4652(199908)180:2<173::AID-JCP5>3.0.CO;2-Y.


The regulation of tyrosine phosphorylation represents a key mechanism governing cell proliferation. In fibroblasts, inputs from both growth factor and extracellular matrix receptors are required for cell division. Triggering such receptors induces a wave of tyrosine phosphorylation on key signaling molecules, culminating in the activation of cyclin-dependent kinases and cell cycle progression. In general, protein tyrosine kinases stimulate, while protein tyrosine phosphatases inhibit, such cell proliferation pathways. The role of protein tyrosine kinases in mitogenesis has been extensively studied, but the identity and targets of the protein tyrosine phosphatases that regulate cell growth are not well described. In this review, I will survey recent advances in the identification and regulation of protein tyrosine phosphatases that downregulate cell proliferation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Division / physiology
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • Humans
  • Mitogens / physiology*
  • Protein Tyrosine Phosphatases / metabolism*
  • Signal Transduction / physiology*


  • Mitogens
  • Protein Tyrosine Phosphatases