Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10815238 | Cellular Signalling | 2014 | 10 Pages |
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.
Keywords
PLCγ2Flavocytochrome b558ERMVav1PAK2GTPasesPAK1PDE2PIXBLNKSLP-76GEFMLCPGAMN-formyl-methionyl-leucyl-phenylalanineSH3fMLPFcεRIPBDauto-inhibitory domainMicroglial cell linePLDNFATGTPB cell Linker proteinGβγIgECDCp21-binding domainIC50phospholipase Cγ2RhoAERKWASPPP2ALIM domain kinase 1ezrin/radixin/moesinguanosine-5′-triphosphateras homolog gene family, member AROSAdenosine-triphosphateATPNADPH oxidaseImmunoglobulin ECytoskeletal dynamicsRhomyosin light chainCAMB-cellT-cellnuclear factor of activated T-cellsPhosphodiesterase 2Phospholipase Dphosphoglycerate mutasefragment crystallizableCardiacB lymphocytesT lymphocytesCell migrationNADHNckhalf maximal inhibitory concentrationnicotinamide adenine dinucleotidenicotinamide adenine dinucleotide phosphate-oxidaseSrc homology 3Wiskott–Aldrich syndrome proteinprotein phosphatase 2CalmodulinAIDextracellular-signal-regulated kinaseReactive oxygen species
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Authors
Domenico M. Taglieri, Masuko Ushio-Fukai, Michelle M. Monasky,