Regulatory subunit type I-? of protein kinase A (PRKAR1A): A tumor-suppressor gene for sporadic thyroid cancer

2002 ◽  
Vol 35 (2) ◽  
pp. 182-192 ◽  
Author(s):  
Fabiano Sandrini ◽  
Ludmila Matyakhina ◽  
Nicholas J. Sarlis ◽  
Lawrence S. Kirschner ◽  
Constantine Farmakidis ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Kinase ◽  
Tumor Suppressor ◽  
Protein Kinase A ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Regulatory Subunit ◽  
Type I ◽  
Kinase A

Protein kinase A and its role in human neoplasia: the Carney complex paradigm.

2004 ◽  
Vol 11 (2) ◽  
pp. 265-280 ◽  
Author(s):  
I Bossis ◽  
A Voutetakis ◽  
T Bei ◽  
F Sandrini ◽  
K J Griffin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cushing Syndrome ◽  
Skin Pigmentation ◽  
Suppressor Gene ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Extensive Literature ◽  
Bilateral Adrenal Hyperplasia ◽  
Kinase A

The type 1 alpha regulatory subunit (R1alpha) of cAMP-dependent protein kinase A (PKA) (PRKAR1A) is an important regulator of the serine-threonine kinase activity catalyzed by the PKA holoenzyme. Carney complex (CNC) describes the association 'of spotty skin pigmentation, myxomas, and endocrine overactivity'; CNC is in essence the latest form of multiple endocrine neoplasia to be described and affects the pituitary, thyroid, adrenal and gonadal glands. Primary pigmented nodular adrenocortical disease (PPNAD), a micronodular form of bilateral adrenal hyperplasia that causes a unique, inherited form of Cushing syndrome, is also the most common endocrine manifestation of CNC. CNC and PPNAD are genetically heterogeneous but one of the responsible genes is PRKAR1A, at least for those families that map to 17q22-24 (the chromosomal region that harbors PRKAR1A). CNC and/or PPNAD are the first human diseases to be caused by mutations in one of the subunits of the PKA holoenzyme. Despite the extensive literature on R1alpha and PKA, little is known about their potential involvement in cell cycle regulation, growth and/or proliferation. The presence of inactivating germline mutations and the loss of its wild-type allele in CNC lesions indicated that PRKAR1A could function as a tumor-suppressor gene in these tissues. However, there are conflicting data in the literature about PRKAR1A's role in human neoplasms, cancer cell lines and animal models. In this report, we review briefly the genetics of CNC and focus on the involvement of PRKAR1A in human tumorigenesis in an effort to reconcile the often diametrically opposite reports on R1alpha.

Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex

10.1038/79238 ◽  
2000 ◽  
Vol 26 (1) ◽  
pp. 89-92 ◽  
Author(s):  
Lawrence S. Kirschner ◽  
J. Aidan Carney ◽  
Svetlana D. Pack ◽  
Susan E. Taymans ◽  
Christoforos Giatzakis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Type I ◽  
Gene Encoding ◽  
Kinase A

scholarly journals Minireview: PRKAR1A: Normal and Abnormal Functions

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5452-5458 ◽  
Author(s):  
Ioannis Bossis ◽  
Constantine A. Stratakis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Skin Pigmentation ◽  
Suppressor Gene ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Type I ◽  
Dependent Protein ◽  
Main Component ◽  
Degree Of Differentiation

Abstract The type 1α regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA) (coded by the PRKAR1A gene) is the main component of type I PKA, which regulates most of the serine-threonine kinase activity catalyzed by the PKA holoenzyme in response to cAMP. Carney complex (CNC), or the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, is a multiple endocrine (and not only) neoplasia syndrome that is due to PRKAR1A-inactivating mutations. The R1α protein and PRKAR1A mRNA have been found to be up-regulated in a series of cell lines and human and rodent neoplasms, suggesting this molecule’s involvement in tumorigenesis and its potential role in cell cycle regulation, growth, and/or proliferation. Alterations in PKA activity elicit a variety of effects depending on the tissue, developmental stage, degree of differentiation, and cAMP levels. In addition, RIα may have functions independent of PKA. The presence of inactivating germline mutations and the loss of its wild-type allele in some CNC lesions indicate that PRKAR1A might function as a tumor suppressor gene in these tissues, but could PRKAR1A be a classic tumor suppressor gene? Probably not, and this review explains why.

scholarly journals Interactions between the Regulatory Subunit of Type I Protein Kinase A and p90 Ribosomal S6 Kinase1 Regulate Cardiomyocyte Apoptosis

2013 ◽  
Vol 85 (2) ◽  
pp. 357-367 ◽  
Author(s):  
Xianlong Gao ◽  
Brian Lin ◽  
Sakthivel Sadayappan ◽  
Tarun B. Patel
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cardiomyocyte Apoptosis ◽  
Regulatory Subunit ◽  
Type I ◽  
Kinase A

scholarly journals Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1361
Author(s):  
Maira Zorzan ◽  
Claudia Del Vecchio ◽  
Stefania Vogiatzis ◽  
Elisa Saccon ◽  
Cristina Parolin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Lentiviral Vectors ◽  
Brain Parenchyma ◽  
Regulatory Subunit ◽  
Glioblastoma Cells ◽  
Cellular Models ◽  
Therapeutic Setting ◽  
Promising Target ◽  
Kinase A

Glioblastoma is the most malignant and most common form of brain tumor, still today associated with a poor 14-months median survival from diagnosis. Protein kinase A, particularly its regulatory subunit R2Alpha, presents a typical intracellular distribution in glioblastoma cells compared to the healthy brain parenchyma and this peculiarity might be exploited in a therapeutic setting. In the present study, a third-generation lentiviral system for delivery of shRNA targeting the regulatory subunit R2Alpha of protein kinase A was developed. Generated lentiviral vectors are able to induce an efficient and stable downregulation of R2Alpha in different cellular models, including non-stem and stem-like glioblastoma cells. In addition, our data suggest a potential correlation between silencing of the regulatory subunit of protein kinase A and reduced viability of tumor cells, apparently due to a reduction in replication rate. Thus, our findings support the role of protein kinase A as a promising target for novel anti-glioma therapies.

The crystal structure of yeast regulatory subunit reveals key evolutionary insights into Protein Kinase A oligomerization

2021 ◽  
pp. 107732
Author(s):  
Nicolás González Bardeci ◽  
Enzo Tofolón ◽  
Felipe Trajtenberg ◽  
Julio Caramelo ◽  
Nicole Larrieux ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Kinase A
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