Enhanced activation of p21-activated kinase 1 in heart failure contributes to dephosphorylation of connexin 43.

ABSTRACT:

Aims

We previously showed decreased cellular coupling and dephosphorylation of the gap junctional protein connexin 43 (Cx43) in left ventricular (LV) myocytes from an arrhythmogenic rabbit model of non-ischaemic heart failure (HF) that was associated with a 2.5-fold increase in the amount of protein phosphatase type 2A (PP2A) co-localized with Cx43. Here, we further explore the molecular mechanisms of enhanced dephosphorylation of Cx43 in HF. p21-activated kinase 1 (PAK1) is a serine-threonine protein kinase that has been shown to activate PP2A.

Methods and results

We found that total PAK1 and activated PAK1 (PAK1-P(Thr423)) were both increased in HF rabbit LV (vs. controls). PAK1 co-immunoprecipitated (co-IP'd) with Cx43 protein and, with HF, co-IP'd PAK1 and PAK1-P(Thr423)

SUBMITTER: Ai X 

PROVIDER: S-EPMC3172982 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature