The frequency window effect of sinusoidal electromagnetic fields in promoting osteogenic differentiation and bone formation involves extension of osteoblastic primary cilia and activation of protein kinase A

2021 ◽  
Author(s):  
Jian Zhou ◽  
Yu hai Gao ◽  
Bao ying Zhu ◽  
Wen fang He ◽  
Gang Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Protein Kinase A ◽  
Electromagnetic Fields ◽  
Primary Cilia ◽  
Window Effect ◽  
Frequency Window ◽  
Kinase A

scholarly journals Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 361
Author(s):  
Han-Yu Wang ◽  
Chun-Hsiang Lin ◽  
Yi-Ru Shen ◽  
Ting-Yu Chen ◽  
Chia-Yih Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Primary Cilia ◽  
Cell Growth And Migration ◽  
Filament Dynamics ◽  
Gtp Binding ◽  
Cilia Formation ◽  
And Migration ◽  
Septin Filament ◽  
Kinase A

Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynamics and ciliogenesis. The Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment with cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation, followed by disruption of septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7‒SEPT7 interaction, but did not affect SEPT7‒SEPT6‒SEPT2 or SEPT4 interaction. Moreover, we noted that SEPT7 interacted with PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.

scholarly journals The regulatory 1α subunit of protein kinase A modulates renal cystogenesis

2017 ◽  
Vol 313 (3) ◽  
pp. F677-F686 ◽  
Author(s):  
Hong Ye ◽  
Xiaofang Wang ◽  
Megan M. Constans ◽  
Caroline R. Sussman ◽  
Fouad T. Chebib ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Signaling Pathways ◽  
Primary Cilia ◽  
Control Cell ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Renal Cystic Disease ◽  
Kinase A

The failure of the polycystins (PCs) to function in primary cilia is thought to be responsible for autosomal dominant polycystic kidney disease (ADPKD). Primary cilia integrate multiple cellular signaling pathways, including calcium, cAMP, Wnt, and Hedgehog, which control cell proliferation and differentiation. It has been proposed that mutated PCs result in reduced intracellular calcium, which in turn upregulates cAMP, protein kinase A (PKA) signaling, and subsequently other proliferative signaling pathways. However, the role of PKA in ADPKD has not been directly ascertained in vivo, although the expression of the main regulatory subunit of PKA in cilia and other compartments (PKA-RIα, encoded by PRKAR1A) is increased in a mouse model orthologous to ADPKD. Therefore, we generated a kidney-specific knockout of Prkar1a to examine the consequences of constitutive upregulation of PKA on wild-type and Pkd1 hypomorphic ( Pkd1RC) backgrounds. Kidney-specific loss of Prkar1a induced renal cystic disease and markedly aggravated cystogenesis in the Pkd1RC models. In both settings, it was accompanied by upregulation of Src, Ras, MAPK/ERK, mTOR, CREB, STAT3, Pax2 and Wnt signaling. On the other hand, Gli3 repressor activity was enhanced, possibly contributing to hydronephrosis and impaired glomerulogenesis in some animals. To assess the relevance of these observations in humans we looked for and found evidence for kidney and liver cystic phenotypes in the Carney complex, a tumoral syndrome caused by mutations in PRKAR1A. These observations expand our understanding of the pathogenesis of ADPKD and demonstrate the importance of PRKAR1A highlighting PKA as a therapeutic target in ADPKD.

Protein kinase A-mediated septin7 phosphorylation disrupts septin filaments and ciliogenesis

2020 ◽  
Author(s):  
Chun-Hsiang Lin ◽  
Ting-Yu Chen ◽  
Yi-Ru Shen ◽  
Chia-Yih Wang ◽  
Pao-Lin Kuo
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Primary Cilia ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Cell Growth And Migration ◽  
Gtp Binding ◽  
Cilia Formation ◽  
Septin Filament ◽  
Kinase A

Abstract Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among these septins, septin7 (SEPT7) is an important component of all septin filaments. Here we showed that protein kinase A (PKA) phosphorylates SEPT7 at Thr197 thus disrupting septin filament dynamics and ciliogenesis. The PKA targeting site at Thr197 of SEPT7 was conserved among species. Treatment of cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation. SEPT7 phosphorylation at Thr197 disrupted septin filament formation by reducing SEPT7-SEPT7 interaction, but not affected SEPT7-SEPT6-SEPT2 or SEPT4 interaction. Besides, overexpression of phosphomimetic SEPT7 mutant (T197E) disrupted endogenous SEPT7 filaments suggesting T197E had dominant negative effect on septin filament polymerization. We also identified SEPT7 interacted with the PKACA2 via the GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.

scholarly journals Linarin promotes osteogenic differentiation by activating the BMP-2/RUNX2 pathway via protein kinase A signaling

2016 ◽  
Vol 37 (4) ◽  
pp. 901-910 ◽  
Author(s):  
JIA LI ◽  
LINGYU HAO ◽  
JUNHUA WU ◽  
JIQUAN ZHANG ◽  
JIANSHENG SU
Keyword(s):  
Protein Kinase ◽  
Osteogenic Differentiation ◽  
Protein Kinase A ◽  
Kinase A
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