The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PAK4  -  p21 protein (Cdc42/Rac)-activated kinase 4

Homo sapiens

Synonyms: KIAA1142, PAK-4, Serine/threonine-protein kinase PAK 4, p21-activated kinase 4
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on PAK4

  • We also show that the phosphatase activity of purified SSH-1L is F-actin dependent and is negatively regulated via phosphorylation by PAK4 [1].
  • We here present a novel cell motility pathway by demonstrating that PAK4 directly interacts with an integrin intracellular domain and regulates carcinoma cell motility in an integrin-specific manner [2].
  • Furthermore, we mapped the PAK4 binding to the membrane-proximal region of integrin beta 5, and identified an integrin-binding domain at aa 505-530 in the COOH terminus of PAK4 [2].
  • Functionally, PAK4 induced integrin alpha v beta 5-mediated, but not beta1-mediated, human breast carcinoma cell migration, while no changes in integrin cell surface expression levels were observed [2].
  • Thus, unlike other members of the PAK family, PAK4 provides a novel link between Cdc42Hs and the actin cytoskeleton [3].

Biological context of PAK4

  • Because cell survival is a key part of tumorigenesis and anchorage-independent growth, we studied whether PAK4 has a role in protecting cells from cell death [4].
  • Although most previous work was carried out with overexpressed PAK4, here we used RNA interference to knock down endogenous PAK4 in cancer cells [4].
  • Furthermore, dominant negative LIMK1 and a mutant cofilin inhibited the specific cytoskeletal and cell shape changes that were induced in response to a recently characterized constitutively activated PAK4 mutant [5].
  • The cellular locations of PAK4 and Cdc42Hs suggest a role for the Golgi in cell morphogenesis [3].
  • Activated PAK4 regulates cell adhesion and anchorage-independent growth [6].

Anatomical context of PAK4

  • Its expression is elevated in many cancer cell lines, and activated PAK4 is highly transforming, suggesting that it plays an important role in tumorigenesis [4].
  • By studying PAK4 knockdown HeLa cells, we demonstrated that endogenous PAK4 is required for anchorage-independent growth [4].
  • Importantly, the reorganization of the actin cytoskeleton is dependent on PAK4 kinase activity and on its interaction with Cdc42Hs [3].
  • PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia [3].
  • Most importantly, fibroblasts expressing activated PAK4 had a morphology that was characteristic of oncogenic transformation [6].

Associations of PAK4 with chemical compounds

  • PAK4 is the most recently identified member of the PAK family of serine/threonine kinases [5].
  • Co-expression of PAK4 and the constitutively active Cdc42HsV12 causes the redistribution of PAK4 to the brefeldin A-sensitive compartment of the Golgi membrane and the subsequent induction of filopodia and actin polymerization [3].

Physical interactions of PAK4

  • PAK4 was shown to interact specifically with LIMK1 in binding assays [5].
  • Our results indicate that PAK4 is required for optimal binding of the scaffold protein TRADD to the activated TNFalpha receptor through both kinase-dependent and kinase-independent mechanisms [4].

Regulatory relationships of PAK4


Other interactions of PAK4

  • PAK5 is structurally most related to PAK4 and PAK6 to make up the PAK-II subfamily [7].
  • In contrast, the group 2 PAKs (PAK4, 5, and 6) lack this autoinhibitory domain and are not activated by Cdc42/Rac binding, and the mechanisms that regulate their kinase activity have been unclear [8].
  • Immunofluorescence experiments revealed that PAK4 and LIMK1 cooperate to induce cytoskeletal changes in C2C12 cells [5].
  • Consequently, activation of several prosurvival pathways, including the NFkappaB and ERK pathways, is reduced in the absence of PAK4 [4].
  • To address this, we studied the role for PAK4 downstream to the tumor necrosis factor (TNF) alpha receptor [4].


  1. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. Soosairajah, J., Maiti, S., Wiggan, O., Sarmiere, P., Moussi, N., Sarcevic, B., Sampath, R., Bamburg, J.R., Bernard, O. EMBO J. (2005) [Pubmed]
  2. P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration. Zhang, H., Li, Z., Viklund, E.K., Strömblad, S. J. Cell Biol. (2002) [Pubmed]
  3. PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia. Abo, A., Qu, J., Cammarano, M.S., Dan, C., Fritsch, A., Baud, V., Belisle, B., Minden, A. EMBO J. (1998) [Pubmed]
  4. PAK4 functions in tumor necrosis factor (TNF) alpha-induced survival pathways by facilitating TRADD binding to the TNF receptor. Li, X., Minden, A. J. Biol. Chem. (2005) [Pubmed]
  5. Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. Dan, C., Kelly, A., Bernard, O., Minden, A. J. Biol. Chem. (2001) [Pubmed]
  6. Activated PAK4 regulates cell adhesion and anchorage-independent growth. Qu, J., Cammarano, M.S., Shi, Q., Ha, K.C., de Lanerolle, P., Minden, A. Mol. Cell. Biol. (2001) [Pubmed]
  7. Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain. Pandey, A., Dan, I., Kristiansen, T.Z., Watanabe, N.M., Voldby, J., Kajikawa, E., Khosravi-Far, R., Blagoev, B., Mann, M. Oncogene (2002) [Pubmed]
  8. Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase. Kaur, R., Liu, X., Gjoerup, O., Zhang, A., Yuan, X., Balk, S.P., Schneider, M.C., Lu, M.L. J. Biol. Chem. (2005) [Pubmed]
WikiGenes - Universities