PAK1 is a novel cardiac protective signaling molecule

  title={PAK1 is a novel cardiac protective signaling molecule},
  author={Yunbo Ke and Xin Wang and Xuhui Jin and R. John Solaro and Ming Lei},
  journal={Frontiers of Medicine},
We review here the novel cardiac protective effects of the multifunctional enzyme, p21-activated kinase 1 (PAK1), a member of a serine/threonine protein kinase family. Despite the large body of evidence from studies in noncardiac tissue indicating that PAK1 activity is key in the regulation of a number of cellular functions, the role of PAK1 in the heart has only been revealed over the past few years. In this review, we assemble an overview of the recent findings on PAK1 signaling in the heart… 

p21-activated kinase 1 (PAK1) as a therapeutic target for cardiotoxicity

It is proposed that PAK1 holds great promise for novel therapeutic strategies to facilitate improvements in the treatment of complex and diverse cardiovascular diseases.

Phosphorylation-dependent activity-based conformational changes in P21-activated kinase family members and screening of novel ATP competitive inhibitors

The detailed conformational readjustements occurring in the PAKs upon phosphorylation-dephosphorylation events may serve as starting point for devising novel drug molecules that are able to target on activity basis.

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Molecular mechanism of various plant‐based interventions screened for cardioprotective effect in ISP‐induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis is surveyed and their probable mechanistic profile is summarized.

Promoting Glucose Transporter-4 Vesicle Trafficking along Cytoskeletal Tracks: PAK-Ing Them Out

New insights are provided into the process of glucose transport and potential new targets for interventions aimed to improve insulin sensitivity and remediate insulin resistance, pre-diabetes, and the progression to type 2 diabetes are yielded.



Pak1 as a Novel Therapeutic Target for Antihypertrophic Treatment in the Heart

It is discovered that the Pak1 activator FTY720, a sphingosine-like analog, was able to prevent pressure overload-induced hypertrophy in wild-type mice without compromising their cardiac functions, suggesting that it may be a potential therapeutic target for the treatment of cardiachypertrophy and heart failure.

Functional integrity of the T-tubular system in cardiomyocytes depends on p21-activated kinase 1.

p21-Activated kinase1 (Pak1) is a negative regulator of NADPH-oxidase 2 in ventricular myocytes.

p21-activated kinase improves cardiac contractility during ischemia-reperfusion concomitant with changes in troponin-T and myosin light chain 2 phosphorylation.

Results of the study provide a basis for targeting a novel pathway, including Pak1, in the therapies for patients with ischemic events and indicate that Pak1-KO hearts have reduced recovery of myocardial performance after global I/R injury concomitant with changes in troponin-T and MLC2 phosphorylation.

Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway.

The role of the Akt signaling pathway is discussed, focusing on the regulation of cardiac growth, contractile function, and coronary angiogenesis, and how this signaling pathway contributes to the development of physiological/pathological hypertrophy and heart failure are discussed.

Roles of PAK family kinases.

  • E. ManserL. Lim
  • Biology, Computer Science
    Progress in molecular and subcellular biology
  • 1999
In binding the active GTP-forms of Cdc42 and Racl, the α-and γ-PAKs also decrease intrinsic GTP hydrolysis and block action of GTPase activating proteins (GAPs).

Pak1 Is Required to Maintain Ventricular Ca 2+ Homeostasis and Electrophysiological Stability Through SERCA2a Regulation in Mice

Findings indicate that Pak1 is required to maintain ventricular Ca 2+ homeostasis and electrophysiological stability and implicate Pak1 as a novel regulator of cardiac SERCA2a through a transcriptional mechanism.

Expression of active p21-activated kinase-1 induces Ca2+ flux modification with altered regulatory protein phosphorylation in cardiac myocytes.

The data indicate that CA-Pak1 expression has significant effects on ventricular myocyte contractility through altered myofilament Ca2+ sensitivity and modification of the [Ca2+]i transient.

PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation.

This work focuses on the current understanding of the way in which different Rho-associated serine/threonine kinases, denoted PAK (p21-activated kinase), MLK (mixed-lineage kinase) and ROK (Rho-kinase), interact with and are regulated by their partner GTPases.