Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain

Akhilesh Pandey, Ippeita Dan, Troels Z. Kristiansen, Norinobu M. Watanabe, Jesper Voldby, Eriko Kajikawa, Roya Khosravi-Far, Blagoy Blagoev, Matthias Mann

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The p21-activated kinase (PAK) family of protein kinases has recently attracted considerable attention as an effector of Rho family of small G proteins and as an upstream regulator of MAPK signalling pathways during cellular events such as re-arrangement of the cytoskeleton and apoptosis. We have cloned a novel human PAK family kinase that has been designated as PAK5. PAK5 contains a CDC42/Rac1 interactive binding (CRIB) motif at the N-terminus and a Ste20-like kinase domain at the C-terminus. PAK5 is structurally most related to PAK4 and PAK6 to make up the PAK-II subfamily. We have shown that PAK5 preferentially binds to CDC42 in the presence of GTP and that CRIB motif is essential for this interaction. PAK5 is a functional protein kinase but unlike PAK-I family kinases (PAK1, 2, and 3), the kinase activity of PAK5 does not seem to require the binding of CDC42. Overexpression of PAK5 activates the JNK kinase pathway but not p38 or ERK pathways. PAK5 transcript is predominantly expressed in brain as revealed by Northern blot and in situ hybridization. The expression pattern of PAK5 is distinct from that of PAK4 and PAK6, suggesting a functional division among PAK-II subfamily kinases based on differential tissue distribution.

Original languageEnglish (US)
Pages (from-to)3939-3948
Number of pages10
JournalOncogene
Volume21
Issue number24
DOIs
StatePublished - May 30 2002
Externally publishedYes

Keywords

  • Brain
  • CDC42
  • JNK
  • p21-activated kinase
  • Ste20

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Pandey, A., Dan, I., Kristiansen, T. Z., Watanabe, N. M., Voldby, J., Kajikawa, E., Khosravi-Far, R., Blagoev, B., & Mann, M. (2002). Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain. Oncogene, 21(24), 3939-3948. https://doi.org/10.1038/sj.onc.1205478