title: Structure, biochemistry, and biology of PAK kinases.
abstract: PAKs, p21-activated kinases, play central roles and act as converging junctions for discrete signals elicited on the cell surface and for a number of intracellular signaling cascades. PAKs phosphorylate a vast number of substrates and act by remodeling cytoskeleton, employing scaffolding, and relocating to distinct subcellular compartments. PAKs affect wide range of processes that are crucial to the cell from regulation of cell motility, survival, redox, metabolism, cell cycle, proliferation, transformation, stress, inflammation, to gene expression. Understandably, their dysregulation disrupts cellular homeostasis and severely impacts key cell functions, and many of those are implicated in a number of human diseases including cancers, neurological disorders, and cardiac disorders. Here we provide an overview of the members of the PAK family and their current status. We give special emphasis to PAK1 and PAK4, the prototypes of groups I and II, for their profound roles in cancer, the nervous system, and the heart. We also highlight other family members. We provide our perspective on the current advancements, their growing importance as strategic therapeutic targets, and our vision on the future of PAKs.
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA; Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India. Electronic address: bcmrxk@gwu.edu.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Sanawar
authors.affiliation: Department of Cell Biology, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang 110122, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang 110122, China. Electronic address: fli@mail.cmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D017398:Alternative Splicing; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009420:Nervous System / Q000201:enzymology* / Q000473:pathology; D009422:Nervous System Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D000072417:Protein Domains; D021381:Protein Transport; D015398:Signal Transduction; D013379:Substrate Specificity; D054462:p21-Activated Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C116367:PAK4 protein, human; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: Cancer; Cytoskeleton remodeling; Heart; Nervous system; PAK; p21-Activated kinase