Cytostatic p21 G Protein-Activated Protein Kinase gamma-PAK

Vitam Horm. 2001;62:167-98. doi: 10.1016/s0083-6729(01)62004-1.

Abstract

The p21-activated protein kinase gamma-PAK, also known as PAK2, has very different properties from the other two highly conserved isoforms of the PAK family, alpha-PAK (PAK1) and beta-PAK (PAK3). gamma-PAK has cytostatic activity, as shown by inhibition of cleavage of early frog embryos following microinjection of gamma-PAK and by inhibition of growth when expressed in mammalian cells. gamma-PAK is activated in response to a variety of stresses including radiation- and chemically-induced DNA damage, hyperosmolarity, addition of sphingosine, serum starvation, and contact inhibition. Activation occurs through at least two signaling pathways, depending on the type of stress, one of which requires phosphoinositide 3-kinase and/or tyrosine kinase activity. During apoptosis gamma-PAK is cleaved by caspase 3 and activated and appears to have a role in the apoptotic response. gamma-PAK is present in the cytosol, associated with the membrane and in secretory granules. A wide variety of substrates have been identified for gamma-PAK. We propose gamma-PAK may be involved in coordinating the stress response, possibly in conjunction with other stress response proteins.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism*
  • Base Sequence
  • Biological Transport
  • Enzyme Activation
  • Humans
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Stress, Physiological / enzymology
  • p21-Activated Kinases

Substances

  • Antineoplastic Agents
  • PAK2 protein, human
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • Oncogene Protein p21(ras)