Role Of P21-activated Kinases Research Articles

P-21 Activated Kinases in Liver Disorders.

The p21 Activated Kinases (PAKs) are serine threonine kinases and play important roles in many biological processes, including cell growth, survival, cytoskeletal organization, migration, and morphology. Recently, PAKs have emerged in the process of liver disorders, including liver cancer, hepatic ischemia-reperfusion injury, hepatitis, and liver fibrosis, owing to their effects in multiple signaling pathways in various cell types. Activation of PAKs promotes liver cancer growth and metastasis and contributes to the resistance of liver cancer to radiotherapy and chemotherapy, leading to poor survival of patients. PAKs also play important roles in the development and progression of hepatitis and other pathological processes of the liver such as fibrosis and ischemia-reperfusion injury. In this review, we have summarized the currently available studies about the role of PAKs in liver disorders and the mechanisms involved, and further explored the potential therapeutic application of PAK inhibitors in liver disorders, with the aim to provide a comprehensive overview on current progress and perspectives of PAKs in liver disorders.

The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?

The p21-activated kinases (PAKs), downstream effectors of Ras-related Rho GTPase Cdc42 and Rac, are serine/threonine kinases. Biologically, PAKs participate in various cellular processes, including growth, apoptosis, mitosis, immune response, motility, inflammation, and gene expression, making PAKs the nexus of several pathogenic and oncogenic signaling pathways. PAKs were proved to play critical roles in human diseases, including cancer, infectious diseases, neurological disorders, diabetes, pancreatic acinar diseases, and cardiac disorders. In this review, we systematically discuss the structure, function, alteration, and molecular mechanisms of PAKs that are involved in the pathogenic and oncogenic effects, as well as PAK inhibitors, which may be developed and deployed in cancer therapy, anti-viral infection, and other diseases. Furthermore, we highlight the critical questions of PAKs in future research, which provide an opportunity to offer input and guidance on new directions for PAKs in pathogenic, oncogenic, and drug discovery research.

The role of p21-activated kinases in pancreatic cancer.

Pancreatic cancer is an aggressive cancer with a poor prognosis and an overall 5-year survival rate of less than 5%. Management has not improved significantly over the last 30 years, and a better understanding of the genetic and molecular changes that occur is urgently required. Many of these changes appear to involve the p21-activated kinases (PAKs). The PAK family consists of 6 isoforms, 2 of which, PAK1 and PAK4, are up-regulated and/or hyperactivated in pancreatic cancer. p21-Activated kinases can mediate many different cellular processes especially those contributing to cancer development and progression. These processes include the regulation of cytoskeletal dynamics and cell adhesion, the evasion of apoptosis, and the promotion of cell survival, proliferation, migration, and invasion. p21-Activated kinases may also be involved in characteristics unique to pancreatic tumors, such as interplay with the pancreatic stroma, the re-emergence of embryonic pathways, and the involvement of a subset of microRNAs and heat shock proteins. This review highlights the potential role of PAKs in pancreatic cancer and provides a foundation for more effective therapeutics to improve our current treatment of pancreatic cancer.

The role of p21-activated kinases in hepatocellular carcinoma metastasis

The p21-activated kinases (PAKs) are downstream effectors of the Rho family small GTPases as well as a wide variety of mitogenic factors and have been implicated in cancer formation, development and metastasis. PAKs phosphorylate a wide spectrum of substrates to mediate extracellular signals and regulate cytoskeletal remodeling, cell motility and survival. In this review, we aim to summarize the findings regarding the oncogenic role and the underlying mechanisms of PAKs signaling in various cancers, and in particular highlight the prime importance of PAKs in hepatocellular carcinoma (HCC) progression and metastasis. Recent studies exploring the potential therapeutic application of PAK inhibitors will also be discussed.

Role of p21-activated kinases in cardiovascular development and function

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.