TY - JOUR
T1 - P21-activated kinase in inflammatory and cardiovascular disease
AU - Taglieri, Domenico M.
AU - Ushio-Fukai, Masuko
AU - Monasky, Michelle M.
N1 - Funding Information:
This work was supported by grants R01HL116976 and R21HL112293 from the National Institutes of Health (to M. U.-F.) and by a Marie Curie International Incoming Fellowship , PIIF-GA-2013-626429 (to M. M. M.).
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - Cardiac
KW - Cell migration
KW - Cytoskeletal dynamics
KW - NADPH oxidase
KW - PAK1
KW - PAK2
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U2 - 10.1016/j.cellsig.2014.04.020
DO - 10.1016/j.cellsig.2014.04.020
M3 - Review article
C2 - 24794532
AN - SCOPUS:84904288300
SN - 0898-6568
VL - 26
SP - 2060
EP - 2069
JO - Cellular Signalling
JF - Cellular Signalling
IS - 9
ER -
