Small heat shock protein 20 (Hsp20) facilitates nuclear import of protein kinase D 1 (PKD1) during cardiac hypertrophy

Sin, Yuan Yan; Martin, Tamara P.; Wills, Lauren P.; Currie, Susan; Baillie, George S.

doi:10.1186/s12964-015-0094-x

Cited by 28 publications

(30 citation statements)

References 28 publications

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“…Disruption of the small heat shock protein 20 (hsp20)-PKD interaction, which chaperones nuclear translocation of PKD1, inhibited nuclear import of PKD and β-AR induced hypertrophy (Sin et al, 2015). In microvascular endothelial cells, PKD1/HDAC7 signaling to FoxO1 initiates proangiogenic and proarteriogenic transcription by repression of CD36 transcription (Ren et al, 2016).…”

Section: Neurohormonal Stress-dependent Pkd Signalingmentioning

confidence: 99%

Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System

Wood

Bossuyt

2017

Front. Pharmacol.

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Protein Kinase D isoforms (PKD 1-3) are key mediators of neurohormonal, oxidative, and metabolic stress signals. PKDs impact a wide variety of signaling pathways and cellular functions including actin dynamics, vesicle trafficking, cell motility, survival, contractility, energy substrate utilization, and gene transcription. PKD activity is also increasingly linked to cancer, immune regulation, pain modulation, memory, angiogenesis, and cardiovascular disease. This increasing complexity and diversity of PKD function, highlights the importance of tight spatiotemporal control of the kinase via protein–protein interactions, post-translational modifications or targeting via scaffolding proteins. In this review, we focus on the spatiotemporal regulation and effects of PKD signaling in response to neurohormonal, oxidant and metabolic signals that have implications for myocardial disease. Precise targeting of these mechanisms will be crucial in the design of PKD-based therapeutic strategies.

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Section: Neurohormonal Stress-dependent Pkd Signalingmentioning

confidence: 99%

Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System

Wood

Bossuyt

2017

Front. Pharmacol.

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“…Flag-tagged wild type and mutated human JAK1 were immunoprecipitated from transfected U4C cells solubilized in immunoprecipitation buffer using Flag M2-Sepharose beads prior to analysis by SDS-PAGE and immunoblotting as previously described (73).…”

Section: Pull-down Assays and Immunoprecipitationsmentioning

confidence: 99%

Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling

et al. 2016

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(T.M.P.); Ian.Salt@glasgow.ac.uk (I.P.S.).Abstract: AMP-activated protein kinase (AMPK) is a pivotal regulator of metabolism at the cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser 515 and Ser 518 ) within the SH2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect which required the presence of Ser 515 and Ser 518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser 515 and Ser 518 abolished AMPKmediated inhibition of JAK-STAT signaling stimulated either by the sIL-6Rα/IL-6 complex or by expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells. Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. Therefore our findings reveal a mechanism by which JAK1 function and inflammatory signaling may be suppressed in response to metabolic stress and provide a mechanistic rationale for the investigation of AMPK activators in a range of diseases associated with enhanced activation of the JAK-STAT pathway.

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“…More recently, PKD1 was identified as a novel partner for HSPB6 and was suggested to bind directly to the HSPB6 to enable HSPB6 phosphorylation at a PKD1 consensus site, which contains serine 16 [77,78]. In the study of Sin et al, cardioprotection was reported to be induced by disruption of PKD1-HSPB6 complex, which should result in a reduction of HSPB6 phosphorylation [78]. The result contradicted the previous notion that increased PKA phosphorylation of HSPB6 functions as a cardioprotective mechanism [79].…”

Section: Anti-hypertrophic Actionmentioning

confidence: 93%

“…Disruption of the PDE4-HSPB6 complex which led to highly phosphorylated endogenous HSPB6 attenuated β-agonist-induced hypertrophy, highlighting the importance of phosphorylation status of HSPB6 on its cardioprotective effects [54]. More recently, PKD1 was identified as a novel partner for HSPB6 and was suggested to bind directly to the HSPB6 to enable HSPB6 phosphorylation at a PKD1 consensus site, which contains serine 16 [77,78]. In the study of Sin et al, cardioprotection was reported to be induced by disruption of PKD1-HSPB6 complex, which should result in a reduction of HSPB6 phosphorylation [78].…”

Section: Anti-hypertrophic Actionmentioning

confidence: 99%

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

Xiao

Zhou

et al. 2017

Cell Physiol Biochem

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HSPB6(Heat shock protein B6), is also referred to as P20/HSP20. Unlike other many other members of sHSP(small Heat shock protein) family, which tend to form high-molecular-mass oligomers, in solution, human HSPB6 only forms dimers. However, it still exhibits chaperon-like activity comparable with that of HSPB5. It is expressed ubiquitously, with high and constitutive expression in muscular tissues. sHSPs characteristically function as molecular chaperones and HSPB6 also has a molecular chaperone activity. HSPB6 is up-regulated in response to diverse cellular stress or damage and protect cells from otherwise lethal conditions. HSPB6 is widely recognized as a principle mediator of cardioprotective signaling and recent studies have unraveled the protective role of HSPB6 in disease or injury to the central nervous system. Moreover, accumulating evidence has implicated HSPB6 as a key mediator of diverse vital physiological processes, such as smooth muscle relaxation, platelet aggregation. The versatility of HSPB6 can be explained by its direct involvement in regulating different client proteins and its ability to form heterooligomer with other sHSPs, which seems to be dependent on HSPB6 phosphorylation. This review focuses on the properties including expression and regulation pattern, phosphorylation, chaperon activity, multiple cellular targets of HSPB6, as well as its possible role in physical and pathological conditions.

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Small heat shock protein 20 (Hsp20) facilitates nuclear import of protein kinase D 1 (PKD1) during cardiac hypertrophy

Cited by 28 publications

References 28 publications

Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System

Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System

Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

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