Biology of the p21-activated kinases

Annu Rev Biochem. 2003;72:743-81. doi: 10.1146/annurev.biochem.72.121801.161742. Epub 2003 Mar 27.


The p21-activated kinases (PAKs) 1-3 are serine/threonine protein kinases whose activity is stimulated by the binding of active Rac and Cdc42 GTPases. Our understanding of the regulation and biology of these important signaling proteins has increased tremendously since their discovery in the mid-1990s. PAKs 1-3 are activated by a variety of GTPase-dependent and -independent mechanisms. This complexity reflects the contributions of PAK function in many cellular signaling pathways and the need to carefully control PAK action in a highly localized manner. PAKs serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signaling, and cell-cycle progression. Consequently, PAKs have also been implicated in a number of pathological conditions and in cell transformation. We propose here a key role for PAK action in coordinating the dynamics of the actin and microtubule cytoskeletons during directional motility of cells, as well as in other functions requiring cytoskeletal polarization.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Movement / physiology
  • Cell Polarity / physiology
  • Cytoskeleton / enzymology
  • Cytoskeleton / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Myosin Type II / metabolism
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / physiology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • p21-Activated Kinases


  • Protein Serine-Threonine Kinases
  • p21-Activated Kinases
  • Myosin Type II