PAK signaling in oncogenesis

The p21-activated kinase (PAK) family of serine/threonine kinases is important in physiological processes including motility, survival, mitosis, transcription and translation. PAKs are evolutionally conserved and widely expressed in a variety of tissues and are often overexpressed in multiple cancer types. Depending on structural and functional similarities, the six members of PAK family are divided into two groups with three members in each group. Group I PAKs are activated by extracellular signals through GTPase-dependent and GTPase-independent mechanisms. In contrast, group II PAKs are constitutively active. Over the years, accumulating data from tissue culture models and human tumors has increased our understanding about the biology of PAK family members. In this review, we have summarized the complex regulation of PAK and its downstream diverse myriads of effectors, which in turn are responsible for the biological effects of PAK family of kinases in cancer cells. Oncogene (2009) 28, 2545-2555; doi: 10.1038/onc.2009.119; published online 25 May 2009