p21-Activated Kinase 4 (PAK4) is a member of the p21-activated kinases (PAKs) family, which are serine/threonine kinases. PAK4 is known for its role as an effector protein for cell division cycle 42 (Cdc42) and is involved in various cellular processes, including cytoskeletal organization, cell morphology, and tumorigenesis .
PAK4 is part of the group B family of PAKs, which also includes PAK5 and PAK6. These kinases are characterized by their ability to bind to and be activated by small GTPases such as Cdc42 and Rac1. Upon activation, PAK4 undergoes autophosphorylation, which enhances its kinase activity and allows it to phosphorylate various downstream targets .
PAK4 is highly expressed and hyperactivated in many cancer types, including breast, gastric, prostate, and pancreatic cancers . It plays a central role in the reorganization of the cytoskeleton, which is crucial for cancer cell migration and invasion. Overexpression of PAK4 has been associated with poor prognosis in non-small cell lung cancer (NSCLC) and promotes migration and invasion of cancer cells .
PAK4 is involved in several intracellular signaling pathways. It acts as a key downstream effector of the K-Ras pathway and the Rho family of GTPases (Rho, Rac, and Cdc42). PAK4 regulates cytoskeleton reorganization, cell proliferation, survival, and motility . It also plays a role in gene transcription pathways by modulating nucleo-cytoplasmic trafficking of β-catenin .
Given its significant role in cancer progression, PAK4 is considered a potential therapeutic target. Inhibiting PAK4 activity could potentially reduce cancer cell proliferation, migration, and invasion. Research is ongoing to develop specific inhibitors that can target PAK4 and its associated signaling pathways .