RGD Reference Report - Regulation of Akt/PKB activity by P21-activated kinase in cardiomyocytes. - Rat Genome Database

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Regulation of Akt/PKB activity by P21-activated kinase in cardiomyocytes.

Authors: Mao, K  Kobayashi, S  Jaffer, ZM  Huang, Y  Volden, P  Chernoff, J  Liang, Q 
Citation: Mao K, etal., J Mol Cell Cardiol. 2008 Feb;44(2):429-34. Epub 2007 Dec 3.
RGD ID: 2299170
Pubmed: PMID:18054038   (View Abstract at PubMed)
PMCID: PMC2278035   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yjmcc.2007.10.016   (Journal Full-text)

Akt/PKB is a critical regulator of cardiac function and morphology, and its activity is governed by dual phosphorylation at active loop (Thr308) by phosphoinositide-dependent protein kinase-1 (PDK1) and at carboxyl-terminal hydrophobic motif (Ser473) by a putative PDK2. P21-activated kinase-1 (Pak1) is a serine/threonine protein kinase implicated in the regulation of cardiac hypertrophy and contractility and was shown previously to activate Akt through an undefined mechanism. Here we report Pak1 as a potential PDK2 that is essential for Akt activity in cardiomyocytes. Both Pak1 and Akt can be activated by multiple hypertrophic stimuli or growth factors in a phosphatidylinositol-3-kinase (PI3K)-dependent manner. Pak1 overexpression induces Akt phosphorylation at both Ser473 and Thr308 in cardiomyocytes. Conversely, silencing or inactivating Pak1 gene diminishes Akt phosphorylation in vitro and in vivo. Purified Pak1 can directly phosphorylate Akt only at Ser473, suggesting that Pak1 may be a relevant PDK2 responsible for AKT Ser473 phosphorylation in cardiomyocytes. In addition, Pak1 protects cardiomyocytes from cell death, which is blocked by Akt inhibition. Our results connect two important regulators of cellular physiological functions and provide a potential mechanism for Pak1 signaling in cardiomyocytes.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase binding  IPIAkt1 (Rattus norvegicus)2299170 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pak1  (p21 (RAC1) activated kinase 1)


Additional Information