Limits...
Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+) homeostasis.

Wang Y, Tsui H, Bolton EL, Wang X, Huang CL, Solaro RJ, Ke Y, Lei M - Front Physiol (2015)

Bottom Line: A series of recent studies report novel roles for Pak1, a key member of the highly conserved family of serine-threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection.This article provides a review of more recent findings on the roles of Pak1 in cardiac Ca(2+) homeostasis.These findings identified crucial roles for Pak1 in cardiomyocyte Ca(2+) handling and demonstrated that it functions through unique mechanisms involving regulation of the post-transcriptional activity of key Ca(2+)-handling proteins, including the expression of Ca(2+)-ATPase SERCA2a, along with the speculative possibility of an involvement in the maintenance of transverse (T)-tubular structure.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Oxford Oxford, UK.

ABSTRACT
A series of recent studies report novel roles for Pak1, a key member of the highly conserved family of serine-threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection. Previous studies had identified Pak1 in the regulation of hypertrophic remodeling that could potentially lead to heart failure. This article provides a review of more recent findings on the roles of Pak1 in cardiac Ca(2+) homeostasis. These findings identified crucial roles for Pak1 in cardiomyocyte Ca(2+) handling and demonstrated that it functions through unique mechanisms involving regulation of the post-transcriptional activity of key Ca(2+)-handling proteins, including the expression of Ca(2+)-ATPase SERCA2a, along with the speculative possibility of an involvement in the maintenance of transverse (T)-tubular structure. They highlight important regulatory functions of Pak1 in Ca(2+) homeostasis in cardiac cells, and identify novel potential therapeutic strategies directed at manipulation of Pak1 signaling for the management of cardiac disease, particularly heart failure.

No MeSH data available.


Related in: MedlinePlus

Regulation of Ca2+ homeostasis by Pak1. Protein kinase PKA and phosphatase PP2A are associated with key Ca2+ handling and regulatory proteins, which in turn are linked to upstream signaling cascades. A balance of protein kinase and phosphatase activities is required to maintain normal cardiac functions. Pak1 also regulates hypertrophic signaling and gene expression of SERCA2a through other signaling pathways by activating its downstream effectors (e.g., JNK). (Liu et al., 2011; Wang et al., 2014a) (NCX: Na+-Ca2+ exchanger, PMCA: Plasma membrane Ca2+ ATPase, JNK: c-Jun N-terminal Kinase).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4362298&req=5

Figure 1: Regulation of Ca2+ homeostasis by Pak1. Protein kinase PKA and phosphatase PP2A are associated with key Ca2+ handling and regulatory proteins, which in turn are linked to upstream signaling cascades. A balance of protein kinase and phosphatase activities is required to maintain normal cardiac functions. Pak1 also regulates hypertrophic signaling and gene expression of SERCA2a through other signaling pathways by activating its downstream effectors (e.g., JNK). (Liu et al., 2011; Wang et al., 2014a) (NCX: Na+-Ca2+ exchanger, PMCA: Plasma membrane Ca2+ ATPase, JNK: c-Jun N-terminal Kinase).

Mentions: In summary, as illustrated in Figure 1, these novel Pak1 effects on Ca2+ homestasis complement previously established actions upon PP2A and the resulting balance between kinase and phosphatase activity in controlling cardiac ion channel activity and rhythmic Ca2+ cycling.


Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+) homeostasis.

Wang Y, Tsui H, Bolton EL, Wang X, Huang CL, Solaro RJ, Ke Y, Lei M - Front Physiol (2015)

Regulation of Ca2+ homeostasis by Pak1. Protein kinase PKA and phosphatase PP2A are associated with key Ca2+ handling and regulatory proteins, which in turn are linked to upstream signaling cascades. A balance of protein kinase and phosphatase activities is required to maintain normal cardiac functions. Pak1 also regulates hypertrophic signaling and gene expression of SERCA2a through other signaling pathways by activating its downstream effectors (e.g., JNK). (Liu et al., 2011; Wang et al., 2014a) (NCX: Na+-Ca2+ exchanger, PMCA: Plasma membrane Ca2+ ATPase, JNK: c-Jun N-terminal Kinase).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362298&req=5

Figure 1: Regulation of Ca2+ homeostasis by Pak1. Protein kinase PKA and phosphatase PP2A are associated with key Ca2+ handling and regulatory proteins, which in turn are linked to upstream signaling cascades. A balance of protein kinase and phosphatase activities is required to maintain normal cardiac functions. Pak1 also regulates hypertrophic signaling and gene expression of SERCA2a through other signaling pathways by activating its downstream effectors (e.g., JNK). (Liu et al., 2011; Wang et al., 2014a) (NCX: Na+-Ca2+ exchanger, PMCA: Plasma membrane Ca2+ ATPase, JNK: c-Jun N-terminal Kinase).
Mentions: In summary, as illustrated in Figure 1, these novel Pak1 effects on Ca2+ homestasis complement previously established actions upon PP2A and the resulting balance between kinase and phosphatase activity in controlling cardiac ion channel activity and rhythmic Ca2+ cycling.

Bottom Line: A series of recent studies report novel roles for Pak1, a key member of the highly conserved family of serine-threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection.This article provides a review of more recent findings on the roles of Pak1 in cardiac Ca(2+) homeostasis.These findings identified crucial roles for Pak1 in cardiomyocyte Ca(2+) handling and demonstrated that it functions through unique mechanisms involving regulation of the post-transcriptional activity of key Ca(2+)-handling proteins, including the expression of Ca(2+)-ATPase SERCA2a, along with the speculative possibility of an involvement in the maintenance of transverse (T)-tubular structure.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Oxford Oxford, UK.

ABSTRACT
A series of recent studies report novel roles for Pak1, a key member of the highly conserved family of serine-threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection. Previous studies had identified Pak1 in the regulation of hypertrophic remodeling that could potentially lead to heart failure. This article provides a review of more recent findings on the roles of Pak1 in cardiac Ca(2+) homeostasis. These findings identified crucial roles for Pak1 in cardiomyocyte Ca(2+) handling and demonstrated that it functions through unique mechanisms involving regulation of the post-transcriptional activity of key Ca(2+)-handling proteins, including the expression of Ca(2+)-ATPase SERCA2a, along with the speculative possibility of an involvement in the maintenance of transverse (T)-tubular structure. They highlight important regulatory functions of Pak1 in Ca(2+) homeostasis in cardiac cells, and identify novel potential therapeutic strategies directed at manipulation of Pak1 signaling for the management of cardiac disease, particularly heart failure.

No MeSH data available.


Related in: MedlinePlus