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Unique catalytic activities and scaffolding of p21 activated kinase-1 in cardiovascular signaling

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posted on 03.01.2014 by Yunbo Ke, Ming Lei, R. John Solaro
P21 activated kinase-1 (Pak1) has diverse functions in mammalian cells. Although a large number of phosphoproteins have been designated as Pak1 substrates from in vitro studies, emerging evidence has indicated that Pak1 may function as a signaling molecule through a unique molecular mechanism - scaffolding. By scaffolding, Pak1 delivers signals through an auto-phosphorylation-induced conformational change without transfer of a phosphate group to its immediate downstream effector(s). Here we review evidence for this regulatory mechanism based on structural and functional studies of Pak1 in different cell types and research models as well as in vitro biochemical assays. We also discuss the implications of Pak1 scaffolding in disease-related signaling processes and the potential in cardiovascular drug development.

Funding

We thank National Institute of Health (USA), UIC CCTS and Medical Research Council (UK) for funding our present research work.

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Publisher Statement

Copyright © 2013 Ke, Lei, Wang and Solaro. This is an open-access article dis- tributed under the terms of the Creative Commons Attribution License (CCBY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are cred- ited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permit- ted which does not comply with these terms. This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.

Publisher

Frontiers

Language

en_US

issn

1663-9812

Issue date

01/09/2013

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