Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene

Oncogene. 2001 Apr 5;20(15):1892-9. doi: 10.1038/sj.onc.1204279.


Protein phosphatase 2A (PP2A) consists of three subunits, A, B and C. The A and B subunits have regulatory functions while C is the catalytic subunit. PP2A core enzyme is composed of subunits A and C, and the holoenzyme of subunits A, B and C. All subunits exist as multiple isoforms or splice variants. The A subunit exists as two isoforms, A alpha and A beta. Here we report about the properties of eight A beta mutants, which were found in human lung and colon cancer. These mutants were reconstructed by site-directed mutagenesis and assayed for their ability to bind B and C subunits. Two mutants showed decreased binding of PR72, a member of the B" family of B subunits, but normal C subunit binding; two mutants exhibited decreased binding of the C subunit and of B"/PR72; and one mutant showed increased binding of both the C subunit and B"/PR72. Of three mutants that behaved like the wild-type A beta subunit, one is a polymorphic variant and another one is altered outside the binding region for B and C subunits. Importantly, we also found that the wild-type A alpha and A beta isoforms, although 85% identical, are remarkably different in their ability to bind B and C subunits. Our findings may have important implications in regard to the role of PP2A as a tumor suppressor.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / prevention & control
  • Humans
  • Isoenzymes / physiology*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / prevention & control
  • Molecular Sequence Data
  • Mutation
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / physiology*
  • Protein Phosphatase 2
  • Protein Subunits


  • Isoenzymes
  • Protein Subunits
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2