Compartmentalized CDK2 is connected with SHP-1 and β-catenin and regulates insulin internalization

Cell Signal. 2011 May;23(5):911-9. doi: 10.1016/j.cellsig.2011.01.019. Epub 2011 Jan 22.


The cyclin-dependant kinase Cdk2 is compartmentalized in endosomes but its role is poorly understood. Here we show that Cdk2 present in hepatic endosome fractions is strictly located in a Triton X-100-resistant environment. The endosomal Cdk2 was found to be associated with the protein tyrosine phosphatase SHP-1, a regulator of insulin clearance, and the actin anchor β-catenin, a known substrate for both Cdk2 and SHP-1. In the plasma membranes and endosome fractions, β-catenin is associated with CEACAM1, also known as regulator of insulin clearance. We show that β-catenin, not CEACAM1, is a substrate for Cdk2. Partial down-modulation of Cdk2 in HEK293 cells increased the rate of insulin internalization. These findings reveal that Cdk2 functions, at least in part, via a Cdk2/SHP-1/β-catenin/CEACAM1 axis, and show for the first time that Cdk2 has the capacity to regulate insulin internalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Detergents / chemistry
  • Endosomes / enzymology
  • Endosomes / metabolism
  • Humans
  • Insulin / metabolism*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • beta Catenin / metabolism*


  • Antigens, CD
  • CD66 antigens
  • Cell Adhesion Molecules
  • Detergents
  • Insulin
  • RNA, Small Interfering
  • beta Catenin
  • Cyclin-Dependent Kinase 2
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6