title: P21-activated kinase in inflammatory and cardiovascular disease.
abstract: P-21 activated kinases, or PAKs, are serine-threonine kinases that serve a role in diverse biological functions and organ system diseases. Although PAK signaling has been the focus of many investigations, still our understanding of the role of PAK in inflammation is incomplete. This review consolidates what is known about PAK1 across several cell types, highlighting the role of PAK1 and PAK2 in inflammation in relation to NADPH oxidase activation. This review explores the physiological functions of PAK during inflammation, the role of PAK in several organ diseases with an emphasis on cardiovascular disease, and the PAK signaling pathway, including activators and targets of PAK. Also, we discuss PAK1 as a pharmacological anti-inflammatory target, explore the potentials and the limitations of the current pharmacological tools to regulate PAK1 activity during inflammation, and provide indications for future research. We conclude that a vast amount of evidence supports the idea that PAK is a central molecule in inflammatory signaling, thus making PAK1 itself a promising prospective pharmacological target.
authors.affiliation: Department of Anesthesia and General Intensive Care Unit, Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 (Milano), Italy. Electronic address: domenico.taglieri@humanitas.it.
authors.forename: Domenico M
authors.initials: DM
authors.lastname: Taglieri
authors.affiliation: Department of Pharmacology, Center for Lung and Vascular Biology, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave. E403 MSB, M/C868, Chicago, IL 60612, USA. Electronic address: mfukai@uic.edu.
authors.forename: Masuko
authors.initials: M
authors.lastname: Ushio-Fukai
authors.affiliation: Cardiovascular Research Center, Humanitas Research Hospital, Via Manzoni 113, Rozzano, 20089 (Milano), Italy. Electronic address: michelle.monasky@humanitasresearch.it.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Monasky
mesh_terms: D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019255:NADPH Oxidases; D020794:Receptor Protein-Tyrosine Kinases; D054462:p21-Activated Kinases
keywords: Cardiac; Cell migration; Cytoskeletal dynamics; NADPH oxidase; PAK1; PAK2