p21-activated kinases in cancer

  title={p21-activated kinases in cancer},
  author={Rakesh Kumar and Anupama E. Gururaj and Christopher J. Barnes},
  journal={Nature Reviews Cancer},
The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of cancers. p21-activated kinases (Paks) are serine/threonine kinases that function as downstream nodes for various oncogenic signalling pathways. Paks are well-known regulators of cytoskeletal remodelling and cell motility, but have recently also been shown to promote cell proliferation, regulate apoptosis and accelerate mitotic… 

The role of p21-activated kinases in hepatocellular carcinoma metastasis

The findings regarding the oncogenic role and the underlying mechanisms of PAKs signaling in various cancers are summarized and the prime importance ofPAKs in hepatocellular carcinoma (HCC) progression and metastasis is highlighted.

p21-activated kinases and gastrointestinal cancer.

Title The role of p 21-activated kinases in hepatocellular carcinomametastasis

The findings regarding the oncogenic role and the underlying mechanisms of PAKs signaling in various cancers are summarized and the prime importance ofPAKs in hepatocellular carcinoma (HCC) progression and metastasis is highlighted.

p21-activated kinases in thyroid cancer.

The current knowledge on the structure and biological functions of both group I and IIPAKs, as well as the roles that PAKs play in oncogenesis and progression, are discussed, with a focus on thyroid cancer and emerging data regarding BRAF/PAK signaling.

p21-activated kinase 1: PAK'ed with potential

The p21-activated kinases (PAKs) are central players in growth factor signaling networks and morphogenetic processes that control proliferation, cell polarity, invasion and actin cytoskeleton

Molecular Pathways: Targeting P21-Activated Kinase 1 Signaling in Cancer—Opportunities, Challenges, and Limitations

Recent findings about the PAK1 molecular pathways in human cancer are summarized and the current status ofPAK1-targeted anticancer therapies are discussed.

PAK Signaling in Oncogenesis

The complex regulation of PAK and its downstream diverse myriads of effectors, which in turn are responsible for the biological effects ofPAK family of kinases in cancer cells are summarized.

PAKs in human disease.

Tracing PAKs from GI inflammation to cancer

The importance of altered PAK activation within GI inflammation is highlighted, its effect on oncogenic signalling is emphasised and PAKs as therapeutic targets of chemoprevention are discussed.



Biology of the p21-activated kinases.

  • G. Bokoch
  • Biology
    Annual review of biochemistry
  • 2003
A key role is proposed 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.

Aurora-kinase inhibitors as anticancer agents

The kinases Aurora-A, -B and -C represent a family of such targets and several small-molecule inhibitors have been shown to block their function and their in vivo antitumour activity has recently been reported.

Dysregulation of phosphatidylinositol 3‐kinase and downstream effectors in human breast cancer

It is concluded that aberrant mitogenic signaling in human breast cancer in vivo involves Pak, p38 MAPK and MAPKAPK2 downstream of PI3‐K, but neither of PKB or p70 S6K, and it is proposed that this pathway may serve as a useful targeting nexus for investigation of small molecule inhibitors inhuman breast cancer.

Requirement for PAK4 in the Anchorage-independent Growth of Human Cancer Cell Lines*

It is demonstrated that PAK4 is frequently overexpressed in human tumor cell lines of various tissue origins and identified serine (Ser-474) as the likely autophosphorylation site in the kinase domain of PAK 4 in vivo, and suggested thatPAK4 activity is required for Ras-driven, anchorage-independent growth.

An essential role of Pak1 phosphorylation of SHARP in Notch signaling

It is demonstrated that Pak1–SHARP interaction plays an essential role in enhancing the corepressor functions of SHARP, thereby modulating Notch signaling in human cancer cells.

The Serine/Threonine Kinase PAK4 Prevents Caspase Activation and Protects Cells from Apoptosis*

Expression of wild-type or constitutively active PAK4 delays the onset of apoptosis in response to tumor necrosis factor α stimulation, UV irradiation, and serum starvation, consistent with an antiapoptotic function.

Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway.

It is shown that endogenous, hyperactive Rac3 is present in highly proliferative human breast cancer-derived cell lines and tumor tissues and suggests an important role for Rac3 and Pak in tumor growth.

The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation

It is shown that the Aurora2 kinase is regulated by proteasome dependent degradation and that Aurora2 phosphorylated on T288 may be targeted for degradation during mitosis.

PAK1 hyperactivation is sufficient for mammary gland tumor formation

Results showed that in a transgenic mouse model, overexpression of catalytically active Pak1 leads to the development of malignant mammary tumors and to a variety of other breast lesions, including focal solid nodules, ductal hyperplasia, and mini-intraductal neoplasm and adenoma.

p21-Activated Kinase 1 Phosphorylates the Death Agonist Bad and Protects Cells from Apoptosis

ABSTRACT Bad is a critical regulatory component of the intrinsic cell death machinery that exerts its death-promoting effect upon heterodimerization with the antiapoptotic proteins Bcl-2 and Bcl-xL.