Document Detail


Use of a decoy peptide to purify p21 activated kinase-1 in cardiac muscle and identification of ceramide-related activation.
MedLine Citation:
PMID:  19707468     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
The p(21) activated kinase-1 (Pak1) is a serine-threonine protein kinase directly activated by Cdc42 and Rac1. In cardiac myocytes, Pak1 activation leads to dephosphorylation of cTnI and C-protein through upregulation of phosphatase-2A (PP2A). Pak1 activity is directly correlated with its autophosphorylation, which occurs upon binding to the small GTPases and to some small organic molecules as well. In this report, we describe a novel method for rapid purification of endogenous Pak1 from bovine ventricle muscle. The method is simple and easy to carry out. The purified Pak1 demonstrated autophosphorylation in vitro that was enhanced by D-erythro-sphingosine-1, N-acetyl-D-erythro-sphingosine (C(2)-ceramide), and N-hexanoyl-D-erythro-sphingosine (C(6)-ceramide). Dihydro-L-threo-sphingosine (saphingol) also had some effect on Pak1 autophosphorylation. The method we developed provides a useful tool to study Pak1 activity and regulation in the heart. Moreover, our results indicate a potential role of the sphingolipids as unique signaling molecules inducing a direct activation of Pak1 that may modulate different cardiac functions.
Authors:
Yunbo Ke; R John Solaro
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biologics : targets & therapy     Volume:  2     ISSN:  1177-5475     ISO Abbreviation:  Biologics     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2009-08-26     Completed Date:  2011-07-14     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  101321511     Medline TA:  Biologics     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  903-9     Citation Subset:  -    
Affiliation:
Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
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