Pak1 phosphorylation enhances cortactin-N-WASP interaction in clathrin-caveolin-independent endocytosis

Traffic. 2010 Aug;11(8):1079-91. doi: 10.1111/j.1600-0854.2010.01075.x. Epub 2010 Apr 28.


Growing evidence indicates that kinases are central to the regulation of endocytic pathways. Previously, we identified p21-activated kinase 1 (Pak1) as the first specific regulator of clathrin- and caveolae-independent endocytosis used by the interleukin 2 receptor subunit (IL-2R). Here, we address the mechanism by which Pak1 regulates IL-2Rbeta endocytosis. First, we show that Pak1 phosphorylates an activator of actin polymerization, cortactin, on its serine residues 405 and 418. Consistently, we observe a specific inhibition of IL-2Rbeta endocytosis when cells overexpress a cortactin, wherein these serine residues have been mutated. In addition, we show that the actin polymerization enhancer, neuronal Wiskott-Aldrich syndrome protein (N-WASP), is involved in IL-2Rbeta endocytosis. Strikingly, we find that Pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with N-WASP. Thus, Pak1, by controlling the interaction between cortactin and N-WASP, could regulate the polymerization of actin during clathrin-independent endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 3 / metabolism
  • Actins / metabolism
  • Animals
  • Caveolins / metabolism*
  • Cell Line
  • Clathrin / metabolism*
  • Cortactin / genetics
  • Cortactin / metabolism*
  • Endocytosis / physiology*
  • Humans
  • Interleukin-2 Receptor beta Subunit / metabolism
  • Phosphorylation
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serine / metabolism
  • Wiskott-Aldrich Syndrome Protein, Neuronal / genetics
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism*
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*


  • Actin-Related Protein 3
  • Actins
  • Caveolins
  • Clathrin
  • Cortactin
  • Interleukin-2 Receptor beta Subunit
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Serine
  • p21-Activated Kinases