Pak protein kinases and their role in cancer

Cancer Metastasis Rev. 2009 Jun;28(1-2):51-63. doi: 10.1007/s10555-008-9168-1.


Some of the characteristics of cancer cells are high rates of cell proliferation, cell survival, and the ability to invade surrounding tissue. The cytoskeleton has an essential role in these processes. Dynamic changes in the cytoskeleton are necessary for cell motility and cancer cells are dependent on motility for invasion and metastasis. The signaling pathways behind the reshaping and migrating properties of the cytoskeleton in cancer cells involve a group of Ras-related small GTPases and their effectors, including the p21-activated kinases (Paks). Paks are a family of serine/threonine protein kinases comprised of six isoforms (Pak 1-6), all of which are direct targets of the small GTPases Rac and Cdc42. Besides their role in cytoskeletal dynamics, Paks have recently been shown to regulate various other cellular activities, including cell survival, mitosis, and transcription. Paks are overexpressed and/or hyperactivated in several human tumors and their role in cell transformation makes them attractive therapeutic targets. Pak-targeted therapeutics may efficiently inhibit certain types of tumors and efforts to identify selective Pak-inhibitors are underway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Transformation, Neoplastic
  • Cytoskeleton / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasms / metabolism*
  • Protein Structure, Tertiary
  • Signal Transduction
  • Substrate Specificity
  • cdc42 GTP-Binding Protein / metabolism
  • p21-Activated Kinases / metabolism*
  • rac GTP-Binding Proteins / metabolism


  • PAK1 protein, human
  • p21-Activated Kinases
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins