scholarly journals Molecular Analysis of the Cyclic AMP-Dependent Protein Kinase A (PKA) Regulatory Subunit 1A (PRKAR1A) Gene in Patients with Carney Complex and Primary Pigmented Nodular Adrenocortical Disease (PPNAD) Reveals Novel Mutations and Clues For Pathophysiology: Augmented PKA Signaling is Associated with Adrenal Tumorigenesis in PPNAD

2002 ◽  
Vol 71 (6) ◽  
pp. 1433-1442 ◽  
Author(s):  
Lionel Groussin ◽  
Lawrence S. Kirschner ◽  
Caroline Vincent-Dejean ◽  
Karine Perlemoine ◽  
Eric Jullian ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Novel Mutations ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Pka Regulatory Subunit ◽  
Kinase A

scholarly journals Phosphorylation of SOX9 by Cyclic AMP-Dependent Protein Kinase A Enhances SOX9's Ability To Transactivate aCol2a1 Chondrocyte-Specific Enhancer

2000 ◽  
Vol 20 (11) ◽  
pp. 4149-4158 ◽  
Author(s):  
Wendong Huang ◽  
Xin Zhou ◽  
Véronique Lefebvre ◽  
Benoit de Crombrugghe
Keyword(s):  
Protein Kinase ◽  
Dna Binding ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Chondrocyte Differentiation ◽  
Phosphorylation Sites ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Kinase A

ABSTRACT Sox9 is a high-mobility-group domain-containing transcription factor required for chondrocyte differentiation and cartilage formation. We used a yeast two-hybrid method based on Son of Sevenless (SOS) recruitment to screen a chondrocyte cDNA library and found that the catalytic subunit of cyclic AMP (cAMP)-dependent protein kinase A (PKA-Cα) interacted specifically with SOX9. Next we found that two consensus PKA phosphorylation sites within SOX9 could be phosphorylated by PKA in vitro and that SOX9 could be phosphorylated by PKA-Cα in vivo. In COS-7 cells cotransfected with PKA-Cα and SOX9 expression plasmids, PKA enhanced the phosphorylation of wild-type SOX9 but did not affect phosphorylation of a SOX9 protein in which the two PKA phosphorylation sites (S64 and S211) were mutated. Using a phosphospecific antibody that specifically recognized SOX9 phosphorylated at serine 211, one of the two PKA phosphorylation sites, we demonstrated that addition of cAMP to chondrocytes strongly increased the phosphorylation of endogenous Sox9. In addition, immunohistochemistry of mouse embryo hind legs showed that Sox9 phosphorylated at serine 211 was principally localized in the prehypertrophic zone of the growth plate, corresponding to the major site of expression of the parathyroid hormone-related peptide (PTHrP) receptor. Since cAMP has previously been shown to effectively increase the mRNA levels of Col2a1 and other specific markers of chondrocyte differentiation in culture, we then asked whether PKA phosphorylation could modulate the activity of SOX9. Addition of 8-bromo-cAMP to chondrocytes in culture increased the activity of a transiently transfected SOX9-dependent 48-bp Col2a1chondrocyte-specific enhancer; similarly, cotransfection of PKA-Cα increased the activity of this enhancer. Mutations of the two PKA phosphorylation consensus sites of SOX9 markedly decreased the PKA-Cα activation of this enhancer by SOX9. PKA phosphorylation and the mutations in the consensus PKA phosphorylation sites of SOX9 did not alter its nuclear localization. In vitro phosphorylation of SOX9 by PKA resulted in more efficient DNA binding. We conclude that SOX9 is a target of cAMP signaling and that phosphorylation of SOX9 by PKA enhances its transcriptional and DNA-binding activity. Because PTHrP signaling is mediated by cAMP, our results support the hypothesis that Sox9 is a target of PTHrP signaling in the growth plate and that the increased activity of Sox9 might mediate the effect of PTHrP in maintaining the cells as nonhypertrophic chondrocytes.

scholarly journals The μ Opioid Agonist Morphine Modulates Potentiation of Capsaicin-Evoked TRPV1 Responses through a Cyclic AMP-Dependent Protein Kinase a Pathway

2006 ◽  
Vol 2 ◽  
pp. 1744-8069-2-22 ◽  
Author(s):  
Irina Vetter ◽  
Bruce D Wyse ◽  
Gregory R Monteith ◽  
Sarah J Roberts-Thomson ◽  
Peter J Cabot
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Opioid Agonist ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Kinase A

scholarly journals PRKAR1A gene analysis and protein kinase A activity in endometrial tumors

2012 ◽  
Vol 19 (4) ◽  
pp. 457-462 ◽  
Author(s):  
A Tsigginou ◽  
E Bimpaki ◽  
M Nesterova ◽  
A Horvath ◽  
S Boikos ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Normal Endometrium ◽  
Protein Levels ◽  
Normal Tissues ◽  
Subunit Expression ◽  
Dependent Protein ◽  
Pka Regulatory Subunit ◽  
Kinase A

PRKAR1A codes for the type 1a regulatory subunit (RIα) of the cAMP-dependent protein kinase A (PKA), an enzyme with an important role in cell cycle regulation and proliferation. PKA dysregulation has been found in various tumors, and PRKAR1A-inactivating mutations have been reported in mostly endocrine neoplasias. In this study, we investigated PKA activity and the PRKAR1A gene in normal and tumor endometrium. Specimens were collected from 31 patients with endometrial cancer. We used as controls 41 samples of endometrium that were collected from surrounding normal tissues or from women undergoing gynecological operations for other reasons. In all samples, we sequenced the PRKAR1A-coding sequence and studied PKA subunit expression; we also determined PKA activity and cAMP binding. PRKAR1A mutations were not found. However, PKA regulatory subunit protein levels, both RIα and those of regulatory subunit type 2b (RIIβ), were lower in tumor samples; cAMP binding was also lower in tumors compared with normal endometrium (P<0.01). Free PKA activity was higher in tumor samples compared with that of control tissue (P<0.01). There are significant PKA enzymatic abnormalities in tumors of the endometrium compared with surrounding normal tissue; as these were not due to PRKAR1A mutations, other mechanisms affecting PKA function ought to be explored.

scholarly journals Cyclic AMP-Dependent Protein Kinase A Regulates the Alternative Splicing of CaMKIIδ

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e25745 ◽  
Author(s):  
Qingqing Gu ◽  
Nana Jin ◽  
Hongzhuan Sheng ◽  
Xiaomin Yin ◽  
Jianhua Zhu
Keyword(s):  
Alternative Splicing ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Kinase A
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